Mercury & Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig’s Disease)

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ALS is a systemic motor neuron disease that affects the corticospinal and corticobulbar tracts, ventral horn motor neurons, and motor cranial nerve nuclei. Approximately 10 percent of ALS cases are of the familial type that has been linked to a mutation of the copper/zinc super oxide dismutase gene (Cu/Zn SOD). The majority of ALS cases are of the sporadic type. Based on studies of groups of monozygous twins, animal studies, and ALS patient case studies, the majority of ALS cases does not appear to be genetic but rather have primarily environmental related causes often affecting genetically susceptible individuals. Mutation of the FUS gene or TPD-43 gene has been shown to be one of the major factors in familial and some sporadic ALS.

ALS is not a unique disease with a single cause or factor, but instead it is a result of damage to motor neurons and the motor neurons’ support system. Spinal and bulbar-onset subtypes of the disease appear to be biochemically different and have differences in mechanisms of causality. Some of the mechanisms of neural damage found in ALS include increased free radical generation/oxidative damage, impaired electron transport, disrupted calcium channel function, reactive astrogliosis and dysfunctional transporters for L-glutamate, neurotoxicity, oxidative damage to mitochondrial DNA/ inhibition of the mitochondrial respiratory chain, autoimmunity, and generalized disruption of metabolism of neuroexciotoxic amino acids like glutamate, aspartate, and NAAG. The mechanisms by which exposure to mercury and other neurotoxic substances cause all of this will be documented.

The main factors determining whether chronic conditions are induced by metals appear to be exposure and genetic, which determines individuals’ immune sensitivity and ability to excrete and detoxify metals. Very low levels of exposure have been found to seriously affect relatively large groups of individuals who are immune-sensitive to toxic metals or have an inability to detoxify metals due to such as deficient sulfoxidation or metallothionein function or other inhibited enzymatic processes related to detoxification or excretion of metals. Those with the genetic allele ApoE4 protein in the blood have been found to detox metals poorly and to be much more susceptible to chronic neurological conditions than those with types ApoE2 or E3. There are also other, similar factors.

Some of the toxic exposures, which have been found to be a factor in ALS-like symptoms, other than mercury include lead, pyretherins, agricultural chemicals, Lyme disease, monosodium glutamate, failed root canal teeth, post-poliomyelitis, pesticides/formaldehyde, and smoking. All have been demonstrated to cause some of the damage listed above that is seen in ALS, and since such exposures are common as is exposure to mercury, such exposures appear to synergistically cause the types of damage seen in ALS. A study of approx. 1000 men and women who died of ALS found that male programmers and laboratory technicians and female machine assemblers may be at increased risk of death from ALS.

This paper will demonstrate that mercury is the most common of toxic substances, which are documented to accumulate through chronic exposure in the neurons affected by ALS and which have been documented to cause all of the conditions and symptoms seen in ALS. It will also be noted that chronic infections such as mycoplasma, echo-7 enterovirus, and candida albicans also usually affect those with chronic immune deficiencies, such as ALS patients, and need to be dealt with in treatment. Some studies have also found persons with chronic exposure to electromagnetic fields to have higher levels of mercury exposure and excretion and higher likelihood of getting chronic conditions like ALS.

Documentation of High Common Exposures and Accumulation of Mercury in Motor Neurons

Amalgam dental fillings are the largest source of mercury in most people with daily exposures documented to commonly be above government healthy guidelines. This is due to continuous vaporization of mercury from amalgam in the mouth, along with galvanic currents from mixed metals in the mouth that deposit the mercury in the gums and oral cavity. Mercury has been found in autopsy studies to accumulate in the brain of those with chronic exposures, and levels are directly proportional to the number of amalgam filling surfaces. Due to the high daily mercury exposure and excretion into home and business sewers of those with amalgam, dental amalgam is also the largest source of the high levels of mercury found in all sewers and sewer sludge, and thus, according to government studies, a significant source of mercury in rivers, lakes, bays, fish, and crops. People also get significant exposure from vaccinations, fish, and dental office vapor.

When amalgam was placed into teeth of monkeys and rats, within one year mercury was found to have accumulated in the brain, trigeminal ganglia, spinal ganglia, kidneys, liver, lungs, hormone glands, and lymph glands. People also commonly get exposures to mercury and other toxic metals such as lead, arsenic, nickel, and aluminum from food, water, and other sources. All of these are highly neurotoxic and are documented to cause neurological damage which can result in chronic neurological conditions over time. Mercury has been found to accumulate preferentially in the primary motor function related areas involved in ALS—such as the brain stem, cerebellum, rhombencephalon, dorsal root ganglia, and anterior horn motor neurons, which enervate the skeletal muscles.

Mercury, with exposure either to vapor or organic mercury, tends to accumulate in the glial cells in a similar pattern, and the pattern of deposition is the same as that seen from morphological changes. Though mercury vapor and organic mercury readily cross the blood-brain barrier, mercury has been found to be taken up into neurons of the brain and CNS without having to cross the blood-brain barrier, since mercury has been found to be taken up and transported along nerve axons as well through calcium and sodium channels and along the olfactory path.

Exposure to inorganic mercury has significant effects on blood parameters and liver function. Studies have found that in a dose dependent manner, mercury exposure causes reductions in oxygen consumption and availability, perfusion flow, biliary secretion, hepatic ATP concentration, and cytochrome P450 liver content, while increasing blood hemolysis products and tissue calcium content and inducing heme oxygenase, porphyria, and platelet aggregation through interfering with the sodium pump.

A direct mechanism involving mercury’s inhibition of cellular enzymatic processes by binding with the hydroxyl radical (SH) in amino acids appears to be a major part of the connection to allergic/immune reactive conditions such as eczema, psoriasis, rheumatoid arthritis, Lupus, Scleroderma, allergies, autism, schizophrenia, as well as autoimmune conditions such as ALS, Alzheimer’s, chronic fatigue, etc. For example, mercury has been found to strongly inhibit the activity of dipeptyl peptidase (DPP IV) which is required in the digestion of the milk protein casein as well as of xanthine oxidase. Additional cellular level enzymatic effects of mercury binding with proteins include blockage of sulfur oxidation processes, enzymatic processes involving Vitamins B6 and B12, effects on the cytochrome-C energy processes, along with mercury’s adverse effects on cellular mineral levels of calcium, magnesium, copper, zinc, and lithium. Along with these blockages of cellular enzymatic processes, mercury has been found to cause additional neurological and immune system effects in many by causing immune/autoimmune reactions.

Recent studies provided a comprehensive review of studies, finding a connection between ALS, toxic metals, and autoimmunity. Studies have found the presence of antibodies in ALS patients that interact with motor neurons, inhibiting the sprouting of axons. Immune complexes have also been found in the spinal cords of ALS patients. T cells, activated microglia, and IgG within the spinal cord may be a primary event that leads to lesions and tissue destruction.

Oxidative stress and reactive oxygen species (ROS) have been implicated as major factors in neurological disorders including ALS, motor neuron disease (MND), CFS, FM, Parkinson’s (PD), Multiple Sclerosis (MS), and Alzheimer’s (AD). Mercury forms conjugate with thiol compounds such as glutathione and cysteine and causes depletion of glutathione, which is necessary to mitigate reactive damage. One study found that insertion of amalgam fillings or nickel dental materials causes a suppression of the number of T-lymphocytes and impairs the T-4/T-8 ratio. Low T4/T8 ratio has been found to be a factor in autoimmune conditions. Mercury-induced lipid peroxidation has been found to be a major factor in mercury’s neurotoxicity, along with leading to decreased levels of glutathione peroxidation and superoxide dismutase (SOD). Only a few micrograms of mercury severely disturb cellular function and inhibit nerve growth. Metalloprotein (MT) has a major role in regulation of cellular copper and zinc metabolism, metals transport and detoxification, free radical scavenging, and protection against inflammation. Mercury inhibits sulfur ligands in MT and, in the case of intestinal cell membranes, inactivates MT that normally binds cuprous ions, thus allowing the buildup of copper to toxic levels in many and malfunction of the Zn/Cu SOD function. Mercury also causes displacement of zinc in MT and SOD, which has been shown to be a factor in neurotoxicity and neuronal diseases. Exposure to mercury results in changes in metalloprotein compounds that have genetic effects, having both structural and catalytic effects on gene expression.

Some of the processes affected by such MT control of genes include cellular respiration, metabolism, enzymatic processes, metal-specific homeostasis, and adrenal stress response systems. Significant physiological changes occur when metal ion concentrations exceed threshold levels. Such MT formation also appears to have a relation to autoimmune reactions in significant numbers of people. Of a population of over 3000 tested by the immune lymphocyte reactivity test, 22% tested positive for inorganic mercury and 8% for methylmercury, but much higher percentages tested positive among autoimmune condition patients. In the MELISA laboratory, 12 out of 13 ALS patients tested showed positive immune reactivity lymphocyte responses to metals in vitro, indicating metals reactivity a likely major factor in their condition. A recent study assessed the possible causes of high ALS rates in Guam and similar areas and the recent decline in this condition. One of the study’s conclusions was that a likely factor for the high ALS rates in Guam and similar areas in the past was chronic dietary deficiency since reduced Ca, Mg and Zn induced excessive absorption of divalent metal cations, such as mercury, accelerates oxidant-mediated neuronal degenerations in a genetically susceptible population. The Veterans Administration concluded that higher levels of veterans of Gulf War I than normal contracted ALS. These veterans were subjected to large exposures of toxic metals in vaccines and other toxic exposures, and there is evidence that aluminum hydroxide in vaccines can cause symptoms seen in ALS.

Programmed cell death (apoptosis) is documented to be a major factor in degenerative neurological conditions like ALS, Alzheimer’s MS, and Parkinson’s. Some of the factors documented to be involved in apoptosis of neurons and immune cells include inducement of the inflammatory cytokine Tumor Necrosis Factor-alpha (TNFa), reactive oxygen species and oxidative stress, reduced glutathione levels, liver enzyme effects, inhibition of protein kinase C and cytochrome P450, nitric oxide and peroxynitrite toxicity, excitotoxicity and lipid peroxidation, excess free cysteine levels, excess glutamate toxicity, excess dopamine toxicity, beta-amyloid generation, increased calcium influx toxicity, DNA fragmentation, and mitochondrial membrane dysfunction.

Chronic neurological conditions such as ALS appear to be primarily caused by chronic or acute brain inflammation. The brain is very sensitive to inflammation. Disturbances in metabolic networks (e.g., immuno-inflammatory processes, insulin-glucose homeostasis, adipokine synthesis and secretion, intra-cellular signaling cascades, and mitochondrial respiration) have been shown to be major factors in chronic neurological conditions. Inflammatory chemicals such as mercury, aluminum, and other toxic metals as well as other excitotoxins, including MSG and aspartame, cause high levels of free radicals, lipid peroxidation, inflammatory cytokines, and oxidative stress in the brain and cardiovascular systems.

In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motor neurons via non-cell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L-glutamate are common hallmarks of ALS pathology. Oxidative and excitotoxic insults exert differential effects on spinal motor neurons and astrocytic glutamate transporters in the progression of ALS. Excitotoxicity in ALS affects both motor neurons and astrocytes, favoring their local interactive degeneration. Mercury and other toxic metals inhibit astrocyte function in the brain and CNS, causing increased glutamate and calcium related neurotoxicity. Mercury and increased glutamate in the plasma activate free radical forming processes like xanthine oxidase which produce oxygen radicals and oxidative neurological damage. Nitric oxide related toxicity caused by peroxynitrite formed by the reaction of NO with superoxide anions, which results in nitration of tyrosine residues in neurofilaments and manganese Superoxide Dismutase (SOD) has been found to cause inhibition of the mitochondrial respiratory chain, inhibition of the glutamate transporter, and glutamate-induced neurotoxicity involved in ALS. A recent study has linked some cases of sporadic ALS with the failure to edit key residues in ionotropic glutamate receptors, resulting in excessive influx of calcium ions into motor neurons which in turn triggers cell death. The study suggests that edited AMPA glutamate (GluR2) receptor subunits serve as gatekeepers for motor neuron survival.

These inflammatory processes damage cell structures, including DNA, mitochondria, and cell membranes. They also activate microglia cells in the brain, which control brain inflammation and immunity. Once activated, the microglia secretes large amounts of neurotoxic substances such as glutamate, an excitotoxin, which adds to inflammation and stimulates the area of the brain associated with anxiety. Inflammation also disrupts brain neurotransmitters, resulting in reduced levels of serotonin, dopamine, and norepinephrine. Some of the main causes of such disturbances that have been documented include vaccines, mercury, aluminum, other toxic metals, MSG, aspartame, etc. High levels of aluminum exposure along with low levels of other minerals such as calcium and magnesium have been documented to cause neurological degeneration and appear to be the cause of high ALS and Parkinson’s in the past in Guam. There is evidence that aluminum hydroxide in vaccines can cause symptoms such as those seen in ALS. Aluminum has been found to be a factor in some Alzheimer’s and Parkinson’s cases.

Programmed cell death (apoptosis) is documented to be a major factor in degenerative neurological conditions like ALS, Alzheimer’s, MS, Parkinson’s, etc. Some of the factors documented to be involved in apoptosis of neurons and immune cells include mitochondrial membrane dysfunction. Mitochondrial DNA mutations or dysfunction is fairly common, found in at least 1 in every 200 people, and toxicity effects affect this population more than those with less susceptibility to mitochondrial dysfunction. Mercury depletion of GSH and damage to cellular mitochondria and the increased lipid peroxidation in protein and DNA oxidation in the brain appear to be a major factor in conditions such as ALS, Parkinson’s disease, autism, etc.

Reduced levels of magnesium and zinc are related to metabolic syndrome, insulin resistance, and brain inflammation and are protective against these conditions. Mercury and cadmium inhibiting magnesium and zinc levels as well as inhibiting glucose transfer are other mechanisms by which mercury and toxic metals are factors in metabolic syndrome and insulin resistance/diabetes. TNFa (tumornecrosis factor-alpha) is a cytokine that controls a wide range of immune cell response in mammals, including apoptosis. This process is involved in inflammatory and degenerative neurological conditions like ALS, MS, Parkinson’s, rheumatoid arthritis, etc. Cell signaling mechanisms like sphingolipids are part of the control mechanism for the TNFa apoptosis mechanism. Glutathione is an amino acid that is a normal cellular mechanism for controlling apoptosis. When glutathione is depleted in the brain, reactive oxidative species increased, and CNS and cell signaling mechanisms are disrupted by toxic exposures such as mercury. Mercury has been shown to induce TNFa, deplete glutathione, and increase glutamate, dopamine, and calcium related toxicity, causing inflammatory effects and cellular apoptosis in neuronal and immune cells. Mercury’s biochemical damage at the cellular level includes:

  • DNA damage;
  • inhibition of DNA and RNA synthesis;
  • alteration of protein structure;
  • alteration of the transport and signaling functions of calcium;
  • inhibition of glucose transport, enzyme function, and transport of other essential nutrients;
  • induction of free radical formation;
  • depletion of cellular glutathione (necessary for detoxification processes);
  • inhibition of glutathione peroxidase enzyme;
  • inhibition of glutamate uptake;
  • induction of peroxynitrite and lipid peroxidation damage;
  • abnormal migration of neurons in the cerebral cortex; and
  • immune system damage.

Exposure to mercury vapor and methylmercury is well documented to commonly cause conditions involving tremors, with populations exposed to mercury experiencing tremor levels on average proportional to exposure level. However bacteria, yeasts, and Vitamin B12 methylate inorganic mercury to methylmercury in the mouth and intestines, and mercury inhibits functional methylation in the body, a necessary process. Mercury exposure causes high levels of oxidative stress/reactive oxygen species (ROS), which has been found to be a major factor in apoptosis and neurological disease, including dopamine or glutamate related apoptosis.

Mercury and quinones form conjugates with thiol compounds such as glutathione and cysteine and cause depletion of glutathione, which is necessary to mitigate reactive damage. Such conjugates are found to be highest in the brain substantia nigra with similar conjugates formed with L-Dopa and dopamine in Parkinson’s disease. Mercury depletion of GSH and damage to cellular mitochondria and the increased lipid peroxidation in protein and DNA oxidation in the brain appear to be a major factor in Parkinson’s disease and a factor in other neurological conditions.

Mercury blocks the immune function of magnesium and zinc, whose deficiencies are known to cause significant neurological effects. The low Zn levels result in deficient CuZnSuperoxide dismutase (CuZnSOD), which in turn leads to increased levels of superoxide due to toxic metal exposure. This is in addition to mercury’s effect on metallothionein and copper homeostasis as previously discussed. Copper is an essential trace metal which plays a fundamental role in the biochemistry of the nervous system. Several chronic neurological conditions involving copper metabolic disorders are well documented like Wilson’s Disease and Menkes Disease. Mutations in the copper/zinc enzyme superoxide dismutase (SOD) have been shown to be a major factor in the motor neuron degeneration in conditions like familial ALS. Exposures to toxic metals such as mercury and cadmium have been found to cause such effects, and similar effects on Cu/Zn SOD have been found to be a factor in other conditions such as autism, Alzheimer’s, Parkinson’s, and non-familial ALS. This condition can result in zinc deficient SOD and oxidative damage involving nitric oxide, peroxynitrite, and lipid peroxidation, which has been found to affect glutamate mediated excitability and apoptosis of nerve cells and effects on mitochondria. These effects can be reduced by zinc supplementation, as well as supplementation with antioxidants and nitric oxide-suppressing agents and peroxynitrite scavengers such as Vitamin C, Vitamin E, lipoic acid, Coenzyme Q10, carnosine, gingko biloba, N-acetyl cysteine, melatonin, etc.

In a study involving over 1 million participants, a 23 percent reduction in the risk of the disease was found among those who used Vitamin E supplements for two to four years and a percent reduction occurred among those who used the supplements for five years or more compared to those who did not supplement with the Vitamin. A 21 percent lower adjusted risk of ALS was noted for people whose intake of Vitamin E was from diet. This effect increased with greater dietary Vitamin E intake among women, with those in the top 25 percent having a 43 percent lower risk than that experienced by those whose intake was lowest.

Vitamin E has attracted significant attention from ALS researchers as a result of its antioxidant properties. Vitamin E protects cell membranes against a process known as lipid peroxidation. Lipid peroxidation is the breakdown of the cell membrane and appears to play a role in degenerative diseases such as ALS. Another study in humans indicated that Vitamin E can help prevent ALS because of its antioxidant properties.

Ceruloplasmin in plasma can be similarly affected by copper metabolism dysfunction, like SOD function, and is often a factor in neurodegeneration. Motor neuron dysfunction and loss in amyotrophic lateral sclerosis (ALS) have been attributed to several different mechanisms, including increased intracellular calcium, glutamate dysregulation and excitotoxicity, oxidative stress and free radical damage, nitric oxide related toxicity caused by peroxynitrite, mitochondrial damage/dysfunction, neurofilament aggregation, and dysfunction of transport mechanisms and autoimmunity. These alterations and effects are not mutually exclusive but rather are synergistic, and increased calcium and altered calcium homeostasis appears to be a common denominator. Mercury forms strong bonds with the -SH groups of proteins causing alteration of the transport of calcium and causes mitochondrial release of calcium. This results in a rapid and sustained elevation in intracellular levels of calcium. Calcium plays a major role in the extreme neurotoxicity of mercury and methylmercury. Both inhibit cellular calcium ATPase and calcium uptake by brain microsomes at very low levels of exposure. Protein Kinase C (PKC) regulates intracellular and extra cellular signals across neuronal membranes, and both forms of mercury inhibit PKC at micro molar levels, as well as inhibiting phorbal ester binding. They also block or inhibit calcium L-channel currents in the brain in an irreversible and concentration dependent manner. Mercury vapor or inorganic mercury exposure affects the posterior cingulate cortex and causes major neurological effects with sufficient exposure. Metallic mercury is much more potent than methylmercury in such actions, with 50 % inhibition in animal studies at 13 ppb. Mercury is seen to be a factor in all of these known mechanisms of neural degeneration seen n ALS and other motor neuron conditions.

Spatial and temporal changes in intracellular calcium concentrations are critical for controlling gene expression and neurotransmitter release in neurons. Mercury alters calcium homeostasis and calcium levels in the brain and affects gene expression and neurotransmitter release through its effects on calcium, etc. Mercury inhibits sodium and potassium (N, K) ATPase in dose dependent manner and inhibits dopamine and norepinephrine uptake by synaptosomes and nerve impulse transfer. Mercury also interrupts the cytochrome oxidase system, blocking the ATP energy function, lowering immune growth factor IGF-I levels and impairing astrocyte function. Astrocytes are common cells in the CNS involved in the feeding and detox of nerve cells. Increases in inflammatory cytokines such as caused by toxic metals trigger increased free radical activity and damage to astrocyte and astrocyte function. IGF-I protects against brain and neuronal pathologies like ALS, MS, and fibromyalgia by protecting the astrocytes from this destructive process Na(+),K(+)-ATPase is a transmembrane protein that transports sodium and potassium ions across cell membranes during an activity cycle that uses the energy released by ATP hydrolysis. Mercury is documented to inhibit Na(+),K(+)-ATPase function at very low levels of exposure. Studies have found that in ALS cases there was a reduction in serum magnesium and RBC membrane Na(+)-K+ ATPase activity and an elevation in plasma serum digoxin. The activity of all serum free radical scavenging enzymes, concentration of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased significantly in ALS, while the concentration of serum lipid peroxidation products and nitric oxide increased. The inhibition of Na+-K+ ATPase can contribute to increase in intracellular calcium and decrease in magnesium, which can result in 1) defective neurotransmitter transport mechanism, 2) neuronal degeneration and apoptosis, 3) mitochondrial dysfunction, 4) defective golgi body function, and 5) protein processing dysfunction. M mercury is a cause of most of these conditions seen in ALS.

Mercury exposure also degrades the immune system, resulting in more susceptibility to viral, bacterial, or parasitic effects along with candida albicans which are often present in those with chronic conditions and require treatment. Four such commonly found in ALS patients are mycoplasma, echo-7 enterovirus, candida albicans, and parasites. One clinic found that over 85% of patients with ALS tested have mycoplasma infection—often M. Pneumoniae, but in Gulf War veterans mostly a manmade variety used in bioterrorism agents—M. fermentans. Mercury from amalgam interferes with production of cytokines that activate macrophage and neutrophils, disabling early control of viruses or other pathogens and leading to enhanced infection. While the others are also being commonly found, mycoplasma has been found in 85% of ALS patients by clinics treating such conditions. Mycoplasma appears to be a cofactor with mercury in the majority of cases and shifts the immune T cell balance toward inflammatory cytokines. Treatment of these chronic infections are required and documented to cause improvement in such patients.

Mercury lymphocytes affect amino acids, such as glutamate in the CNS, and induce CFS-type symptoms, including profound tiredness, musculoskeletal pain, sleep disturbances, gastrointestinal, and neurological problems along with other CFS symptoms and fibromyalgia. Mercury has been found to be a common cause of fibromyalgia, which based on a Swedish survey; fibromyalgia occurs in about 12% of women over 35 and 5.5% of men. ALS patients have been found to have a generalized deficiency in metabolism of the neuroexcitotoxic amino acids like glutamate, aspartate, NAAG, etc.

The brain has elaborate protective mechanisms for regulating neurotransmitters such as glutamate, which is the most abundant of all neurotransmitters. When these protective regulatory mechanisms are damaged or affected, chronic neurological conditions such as ALS can result. Glutamate is the most abundant amino acid in the body and in the CNS acts as excitory neurotransmitter, which also causes inflow of calcium. Astrocytes, a type of cell in the brain and CNS with the task of keeping clean the area around nerve cells, have a function of neutralizing excess glutamate by transforming it to glutamic acid. If astrocytes are not able to rapidly neutralize excess glutamate, then a buildup of glutamate and calcium occurs, causing swelling and neurotoxic effects. Mercury and other toxic metals inhibit astrocyte function in the brain and CNS, causing increased glutamate and calcium related neurotoxicity, which are responsible for much of the fibromyalgia symptoms and a factor in neural degeneration in MS and ALS. This is also a factor in conditions such as CFS, Parkinson’s, and ALS. Animal studies have confirmed that increased levels of glutamate (or aspartate, another amino acid excitory neurotransmitter) cause increased sensitivity to pain, as well as higher body temperature-both found in CFS/fibromyalgia. Mercury and increased glutamate activate free radicals forming processes like xanthine oxidase which produce oxygen radicals and oxidative neurological damage. Nitric oxide related toxicity caused by peroxynitrite formed by the reaction of NO with superoxide anions, which results in nitration of tyrosine residues in neurofilaments and manganese Superoxide Dismutase (SOD) has been found to cause inhibition of the mitochondrial respiratory chain, inhibition of the glutamate transporter, and glutamate-induced neurotoxicity involved in ALS.

In addition to the documentation showing the mechanisms by which mercury causes the conditions and symptoms seen in ALS and other neurodegenerative diseases, many studies of patients with major neurological or degenerative diseases have found direct evidence mercury and amalgam fillings play a major role in development of conditions such as ALS. Such supplements including N-acetylcysteine (NAC), Vitamins E and C, zinc, and creatinine have been found to offer significant protection against cell apoptosis and neurodegeneration in neurological conditions such as ALS. Medical studies and doctors treating chronic conditions like Fibromyalgia have found that supplements which cause a decrease in glutamate or protect against its effects have a positive effect on Fibromyalgia and other chronic neurologic conditions. Some that have been found to be effective include CoQ10, ginkgo biloba and pycnogenol, NAC, Vitamin B6, methylcobalamine, L-carnitine, choline, ginseng, Vitamins C and E, nicotine, and omega 3 fatty acids (fish and flaxseed oil). A study demonstrated protective effects of methylcobalamin, a Vitamin B12 analog, against glutamate-induced neurotoxicity, and similarly for iron in those who are iron deficient.

In a study of the brains of persons dying of ALS, spherical and crescent-shaped introneuronal inclusions(SCI) were distributed in association with each other among the parahippocampal gyrus, dentate gyrus of the hippocampus and amygdala, but not any non-motor-associated brain regions. The occurrence of SCI in both the second and third layers of the parahippocampal gyrus and amygdala was significantly correlated to the presence of dementia in ALS cases. Mercury has been found to accumulate in these areas of the brain and to cause adverse behavioral effects in animal studies and humans.

Another neurological effect of mercury that occurs at very low levels is inhibition of nerve growth factors, for which deficiencies result in nerve degeneration. Only a few micrograms of mercury severely disturb cellular function and inhibit nerve growth. Prenatal or neonatal exposures have been found to have lifelong effects on nerve function and susceptibility to toxic effects. Prenatal mercury vapor exposure that results in levels of only 4 parts per billion in newborn rat brains was found to cause nerve growth deceases and other effects. This is a level that is common in the population with several amalgam fillings or other exposures. There is also evidence that fetal or infant exposure causes delayed neurotoxicity evidenced in serious effect at middle age. Insulin-like-growth factor I (IGF-I) are positively correlated with growth hormone levels and have been found to be the best easily measured marker for levels of growth hormone, but males have been found more responsive to this factor than women.

IGF-I controls the survival of spinal motor neurons affected in ALS during development as well as later in life. IGF-I and insulin levels have been found to be reduced in ALS patients with evidence this is a factor in ALS. Several clinical trials have found IGF-I treatment is effective at reducing the damage and slowing the progression of ALS and Alzheimer’s with no medically important adverse effects. It has also been found that in chronically ill patients the levels of pituitary and thyroid hormones that control many bodily processes are low, and supplementing both thyrotropin-releasing hormone and growth control hormone is more effective at increasing all of these hormone levels in the patient.

Extremely toxic anaerobic bacteria from root canals or cavitations formed at incompletely healed tooth extraction sites have also been found to be common factors in fibromyalgia and other chronic neurological conditions such as Parkinson’s and ALS, with condensing osteitis which must be removed with a surgical burr along with 1 mm of bone around it. Cavitations have been found in 80% of sites from wisdom tooth extractions tested and 50% of molar extraction sites tested. The incidence is likely somewhat less in the general population. Medical studies and doctors treating fibromyalgia have found that supplements which cause a decrease in glutamate or protect against its effects have a positive effect on fibromyalgia and other chronic neurologic conditions like ALS. Some that have been found to be effective include Vitamin B6, methylcobalamine, L-carnitine, choline, ginseng, Ginkgo biloba, Vitamins C and E, CoQ10, nicotine, and omega 3 fatty acids (fish and flaxseed oil).

Clinical tests of patients with ALS, MND, Parkinson’s, Alzheimer’s, Lupus (SLE), and rheumatoid arthritis have found that the patients generally have elevated plasma cysteine to sulfate ratios, with the average being 500% higher than controls. This means that these patients have blocked enzymatic processes for converting the basic cellular fuel cysteine to sulfates and glutathione and thus insufficient sulfates available to carry out necessary bodily processes. Mercury has been shown to diminish and block sulfur oxidation and thus reducing glutathione levels which is the part of this process involved in detoxifying and excretion of toxics like mercury. Glutathione is produced through the sulfur oxidation side of this process. Low levels of available glutathione have been shown to increase mercury retention and increase toxic effects, while high levels of free cysteine have been demonstrated to make toxicity due to inorganic mercury more severe. The deficiency in conjugation and detoxification of sulfur-based toxins in the liver results in toxic metabolites and progressive nerve damage over time. Mercury has also been found to play a part in inducing intolerance and neuronal problems through blockage of the P-450 enzymatic process. Patients with some of these conditions have found that bathing in Epsom salts (magnesium sulfate) offers temporary relief for some of their symptoms by providing sulfates that avoid the blocked metabolic pathway. A test that some doctors treating conditions like ALS usually prescribe to measure the cysteine to sulfate ratio and other information useful in diagnosis and treatment is the Great Smokies Diagnostic Lab’s comprehensive liver detox test. The test results come with some recommendations for treatment. A hair test for toxic metals is also usually ordered to determine toxic exposures that might be involved. A more definitive test such as MELISA for immune reactivity to toxics is available by sending blood to a European lab. Other labs also have other useful tests such as Immune Reactivity Bio-compatibility Tests, ELISA, organic acid panels, or amino acid panels. Treatment using IV glutathione, Vitamin C, and minerals has been found to be very effective in the stabilizing and amelioration of some of these chronic neurological conditions by neurologist such as Perlmutter in Florida. In one subtype of ALS, damaged, blocked, or faulty enzymatic superoxide dismutase (SOD) processes appear to be a major factor in cell apoptosis involved in the condition. Mercury is known to damage or inhibit SOD activity.

Prevention and Treatment of ALS

Tick-borne encephalitis, such as Lyme disease, has been found to cause ALS symptoms in a significant portion of untreated acute cases. Lyme disease is widespread in the U.S. Large numbers of patients diagnosed with ALS and other neurological conditions have been found to have treatable tick-borne encephalitis, and many have recovered after treatment. Anyone diagnosed with degenerative neurological symptoms should investigate the possibility of Lyme disease or post-polio encephalitis. Poliomyelitis also has a chronic state that resembles ALS.

Since elevated plasma cysteine has been reported in some ALS patients, sulfite and cysteine toxicity may be involved in other cases of ALS. Patients with ALS with nonmutant-SOD should be tested for sulfite toxicity, cysteine, glutamate and GSH levels, and whether they have low levels of GSH metabolism enzymes. During the time when strict dietary and supplement measures normalized a patient’s whole blood GSH, blood cysteine, and urine sulfite, the patient did not experience additional physical decline.

Total dental revision (TDR), which includes replacing amalgam fillings, extracting root canaled teeth, and treating cavitations, has been found to offer significant health improvements to many with ALS and other autoimmune conditions. Root canals and cavitations have been found to harbor anaerobic bacteria which give off toxins of extreme toxicity which block enzymatic processes at the cellular level causing degenerative processes according to the medical labs that do the tests, similar to mercury’s effects but in some cases even more toxic. IGF-1 treatments have also been found to alleviate some of the symptoms of ALS.

Medical studies and doctors treating fibromyalgia have found that supplements which cause a decrease in glutamate or protect against its effects have a positive effect on fibromyalgia. Some that have been found to be effective in treating metals related autoimmune conditions include Vitamin B6, CoenzymeQ10, methylcobalamine, SAMe, L-carnitine, choline, ginseng, Ginkgo biloba, Vitamins C and E, nicotine, and omega 3 fatty acids (fish and flaxseed oil).

One dentist with severe symptoms similar to ALS improved after treatment for mercury poisoning, and others treated for mercury poisoning or using TDR have also recovered or significantly improved. The Edelson Clinic in Atlanta, which treats ALS patients reports similar experience, and the Perlmutter Clinic has also had some success with treatment of ALS and other degenerative neurological conditions.

While there are many studies documenting effectiveness of chemical chelators like DMSA and DMPS at reducing metals levels and alleviating adverse effects for most conditions, and many thousands of clinical case results; there is also some evidence from animal studies that these chelators can result in higher levels of mercury in the motor neurons in the short term which might be a problem for ALS patients. Thus other detox options might be preferable for ALS patients until enough clinical evidence is available treating ALS patients with them with mercury toxicity. Another chelator used for clogged arteries, EDTA, forms toxic compounds with mercury and can damage brain function. Use of EDTA may need to be restricted in those with high Hg levels.

N-acetyl cysteine (NAC) has been found to be effective at increasing cellular glutathione levels and chelating mercury. Experienced doctors have also found additional zinc to be useful when chelating mercury as well as counteracting mercury’s oxidative damage. Zinc induces metallothionein which protects against oxidative damage and increases protective enzyme activities and glutathione which tend to inhibit lipid peroxidation and suppress mercury toxicity. Also lipoic acid, LA, has been found to dramatically increase excretion of inorganic mercury (over 12 fold), but to cause decreased excretion of organic mercury and copper. Lipoic acid has a protective effect regarding lead or inorganic mercury toxicity through its antioxidant properties, but should not be used with high copper until copper levels are reduced. LA and NAC (N-acetyl cysteine) also increase glutathione levels and protect against superoxide radical/peroxynitrite damage, so thus have an additional neuro-protective effect. Zinc is a mercury and copper antagonist and can be used to lower copper levels and protect against mercury damage. Lipoic acid has been found to have protective effects against cerebral ischemic-reperfusion, excitotoxic amino acid (glutamate) brain injury, mitochondrial dysfunction, diabetic neuropathy.

Antioxidants such as carnosine, Coenzyme Q10, Vitamins B, C, E & D, gingko biloba, superoxide dismutase (SOD), N-acetyl-cysteine (NAC), Alpha Lipoic Acid, and pycnogenol have also been found protective against degenerative neurological conditions. Other supplements found to be protective against neuronal degenerative conditions include EFAs, DHEA, magnesium, Vitamin B1 & B5, hydergine, and octacosanol. Such supplements only offer limited protection and reductions in progression of ALS without other measures that deal with underlying mechanisms of causality. In a study involving over 1 million participants, a 23 percent reduction in the risk of the disease was found among those who used Vitamin E supplements for two to four years, and a 36 percent reduction occurred among those who used the supplements for five years or more compared to those who did not supplement with the vitamins.

Other supplements that appear useful in conditions involving neurotoxicity or muscle function degeneration include creatine and lithium. In the motor cortex of the ALS group the N-acetylaspartate (NAA)/creatine metabolite ratio was lower than in the control group, indicating NAA loss. Upon creatine supplementation, the researchers observed in that creatine supplementation causes an increase in the diminished NAA levels in ALS motor cortex as well as an increase of choline levels in both ALS and control motor cortices. This indicates an improvement in function of the pathological ALS skeletal muscles related to changes of mitochondrial respiratory chain which appears to affect motor neuron survival. In another study by the NAS, lithium carbonate at 150 mg twice daily significantly reduced the degeneration of ALS patients. A recent study demonstrated that combined treatment with lithium and valproic acid elicits synergistic neuro-protective effects against glutamate excitotoxicity in cultured brain neurons. Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model. Methylcobalamin and SAMe have also been found to provide some protection against neurotoxicity. Two experimental treatments for ALS that has shown some effectiveness at reducing disease progression is recombinant human insulin-like growth factor and Orap (Pimozide).


  1. Hussain S, et al. Mercuric chloride and induced reactive oxygen species and its effect on antioxidant enzymes in different regions of rat brains. J Environ Sci Health B. 1997; 32(3): 395-409.
  2. Bulat P. Activity of Gpx and SOD in workers occupationally exposed to mercury. Arch Occup Environ Health. 1998; 71: 37-9.
  3. Stohs SJ, Bagchi D. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med. 1995; 18(2): 321-36.
  4. Jay D. Glutathione inhibits SOD activity of Hg. Arch Inst Cardiol Mex. 1998; 68(6): 457-61.
  5. El-Demerdash FM. Effects of selenium and mercury on the enzymatic activities and lipid peroxidation in brain, liver, and blood of rats. J Environ Sci Health B. 2001; 36(4): 489-99.
  6. Tan S, et al. Oxidative stress induces programmed cell death in neuronal cells. J Neurochem. 1998; 71(1): 95-105.
  7. Matsuda T, Takuma K, Lee E, et al. Apoptosis of astroglial cells. Nippon Yakurigaku Zasshi. 1998; 112(1): 24.
  8. Lee YW, Ha MS, Kim YK. Role of reactive oxygen species and glutathione in inorganic mercury-induced injury in human glioma cells. Neurochem Res. 2001 Nov; 26(11): 1187-93.
  9. Ortiz D, Rogers E, Shea TB. Multiple aspects of homocysteine neurotoxicity: Glutamate excitotoxicity, kinase hyperactivation and DNA damage. J Neurosci Res. 2002; 70(5): 694-702.
  10. Galic N, Ferencic Z, et al. Dental amalgam mercury exposure in rats. Biometals. 1999; 12(3): 227-31.
  11. Arvidson B, Arvidsson J, Johansson K. Mercury deposits in neurons of the trigeminal ganglia after insertion of dental amalgam in rats. Biometals. 1994; 7(3): 261-3.
  12. Danscher G, Horsted-Bindslev P, Rungby J. Traces of mercury in organs from primates with amalgam fillings. Exp Mol Pathol. 1990; 52(3): 291-9.
  13. Hahn L, et al. Distribution of mercury released from amalgam fillings into monkey tissues. FASEB J. 1990; 4: 5536.
  14. Goyer RA, Toxic effects of metals. In: Caserett, Doull, eds. Toxicology-The Basic Science of Poisons. New York: McGraw-Hill Inc.; 1993.
  15. Goodman, Gillman. The Pharmacological Basis of Therapeutics. New York: Mac Millan Publishing Company; 1985.
  16. Schmidt F, et al. Mercury in urine of employees exposed to magnetic fields. Tidsskr Nor Laegeforen. 1997; 117(2): 199-202.
  17. Sheppard AR, Eisenbud M. Biological Effects of Electric and Magnetic Fields of Extremely Low Frequency. New York University Press; 1977.
  18. Ortendahl TW, Hogstedt P, Holland RP. Mercury vapor release from dental amalgam in vitro caused by magnetic fields generated by CRT’s. Swed Dent J. 1991: 31.
  19. Markovich, et al. Heavy metals (Hg, Cd) inhibit the activity of the liver and kidney sulfate transporter Sat-1. Toxicol Appl Pharmacol. 1999; 154(2): 181-7.
  20. McFadden SA. Xenobiotic metabolism and adverse environmental response: Sulfur dependent detox pathways. Toxicology. 1996; 111(1-3): 43-65.
  21. Langley-Evans SC, et al. SO2: A potent glutathion depleting agent. Comp Biochem Physiol Pharmocol Toxicol Endocrinol. 1996; 114(2): 89-98.
  22. Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in low-functioning & autistic children. Biol Psychiatry. 1999; 46(3): 420-4.
  23. Henriksson J, Tjalve H. Uptake of inorganic mercury in the olfactory bulbs via olfactory pathways in rats. Environ Res. 1998; 77(2): 13-40.
  24. Huggins HA, Levy, TE. Uniformed Consent: The Hidden Dangers in Dental Care. Hampton Roads Publishing; 1999.
  25. Huggins H. It’s All in Your Head. Avery Publishing; 1993.
  26. Rodgers JS, Hocker JR, et al. Mercuric ion inhibition of eukaryotic transcription factor binding to DNA. Biochem Pharmacol. 2001; 61(12): 1543-50.
  27. Hansen K, et al. A survey of metal induced mutagenicity in vitro and in vivo. J Amer Coll Toxicol. 1984; 3: 381-430.
  28. Knapp LT, Klann E. Superoxide-induced stimulation of protein kinase C via thiol modification and modulation of zinc content. J Biol Chem. 2000.
  29. Jenner P. Oxidative mechanisms in PD. Mov Disord. 1998; 13(1): 24-34.
  30. Rajanna B, et al. Modulation of protein kinase C by heavy metals. Toxicol Lett. 1995; 81(2-3): 197-203.
  31. Badou A, et al. HgCl2-induced IL-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels. J Biol Chem. 1997; 272(51): 32411-8.
  32. Veprintsev DB. Pb2+ and Hg2+ binding to lactalbumin. Biochem Mol Biol. 1996; 39(6): 1255.
  33. Buzard GS, Kasprzak KS. Possible roles of nitric oxide and redox cell signaling in metal-induced toxicity and carcinogenesis: A review. Environ Pathol Toxicol Oncol. 2000; 19(3): 179-99.
  34. Arvidson K. Corrosion studies of dental gold alloy in contact with amalgam. Swed. Dent. J. 1984; 68: 135-139.
  35. Skinner, EW. The Science of Dental Materials. 4th ed. Philadelphia: W. B. Saunders; 1957.
  36. Kingman A, Albertini T, Brown LJ. Mercury concentrations in urine and blood associated with amalgam exposure in the U.S. military population. J Dent Res. 1998; 77(3): 461-71.
  37. Lund ME, et al. Treatment of acute MeHg poisoning by NAC. J Toxicol Clin Toxicol. 1984; 22(1): 31-49.
  38. Livardjani F, Ledig M, Kopp P, Dahlet M, Leroy M, Jaeger A. Lung and blood superoxide dismutase activity in mercury vapor exposed rats: Effect of acetylcysteine treatment. Toxicology. 1991; 66(3): 289-95.
  39. Nicole A, et al. Direct evidence for glutathione as mediator of apoptosis in neuronal cells. Biomed Pharmacother. 1998; 52(9): 349-55.
  40. Spencer JP, et al. Cysteine & GSH in PD, mechanisms involving ROS. J Neurochem. 1998; 71(5): 2112-22.
  41. Bains JS, et al. Neurodegenerative disorders in humans and role of glutathione in oxidative stress mediated neuronal death. Brain Res Rev. 1997; 25(3): 335-58.
  42. Medina S, Martinez M, Hernanz A. Antioxidants inhibit the human cortical neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42. Free Radic Res. 2002; 36(11): 1179-84.
  43. Pocernich CB, et al. Glutathione elevation and its protective role in acrolein-induced protein damage in synaptosomal membranes: relevance to brain lipid peroxidation in neurodegenerative disease. Neurochem Int. 2001; 39(2): 141-9.
  44. Offen D, et al. Use of thiols in treatment of PD. Exp Neurol. 1996; 141(1): 32-9.
  45. Pearce RK, Owen A, Daniel S, Jenner P, Marsden CD. Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease. J Neural Transm. 1997; 104(6-7): 661-77.
  46. Shen XM, et al. Neurobehavioral effects of NAC conjugates of dopamine: Possible relevance for Parkinson’s disease. Chem Res Toxicol. 1996; 9(7): 1117-26.
  47. Li H, Shen XM, Dryhurst G. Brain mitochondria catalyze the oxidation of 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1) to intermediates that irreversibly inhibit complex I and scavenge glutathione: Potential relevance to the pathogenesis of Parkinson’s disease. J Neurochem. 1998; 71(5): 2049-62.
  48. Araragi S, Sato M, et al. Mercuric chloride induces apoptosis via a mitochondrial-dependent pathway in human leukemia cells. Toxicology. 2003; 184(1): 1-9.
  49. Stejskal VDM, et al. Mercury-specific lymphocytes: An indication of mercury allergy in man. J Of Clinical Immunology. 1996; 16(1): 31-40.
  50. Stejskal VDM, et al. MELISA: Tool for the study of metal allergy. Toxicology In Vitro. 1994; 8(5): 991-1000.
  51. Bjorkman L, et al. Mercury in saliva and feces after removal of amalgam fillings. Toxicol App Pharmocol. 1997; 144(1): 156-62.
  52. Veltman JC, et al. Alterations of heme, cytochrome P-450, and steroid metabolism by mercury in rat adrenal gland. Arch Biochem Biophys. 1986; 248(2): 467-78.
  53. Riedl AG, et al. P-450 and hemeoxygenase enzymes in the basal ganglia and their role in Parkinson’s disease. Adv Neurol. 1999; 80: 271-86.
  54. Zamm AV. Dental mercury: A factor that aggravates and induces xenobiotic intolerance. J Orthmol Med. 1991; 6(2): 67-77.
  55. Weiner JA, et al. The relationship between mercury concentration in human organs and predictor variables. Sci Tot Environ. 1993; 138(1-3): 101-115.
  56. Nylander M, et al. Mercury concentrations in the human brain and kidneys and exposure from amalgam fillings. Swed Dent J. 1987; 11: 179-187.
  57. Eggleston, DW et al. Correlation of dental amalgam with mercury in brain tissue. J Prosthet Dent. 1987; 58(6): 704-7.
  58. Tandon L, et al. Elemental imbalance studies by INAA on ALS patients. J Radioanal Nuclear Chem. 1995; 195(1): 13-19.
  59. Mano Y, et al. Mercury in the hair of ALS patients. Rinsho Shinkeigaku. 1989; 29(7): 844-848.
  60. Khare, et al. Trace element imbalances in ALS. Neurotoxicology. 1990; 11: 521-532.
  61. Carpenter DO. Effects of metals on the nervous system of humans and animals. Int J Occup Med Environ Health. 2001; 14(3): 209-18.
  62. Vaccari A, Ruiu S, Mocci I, Saba P, Bernard B. Selected pyrethroid insecticides stimulate glutamate uptake in brain synaptic vesicles. Neuroreport. 1998; 9(15): 3519-23.
  63. Gassner B, Wuthrich A, Scholtysik G, Solioz M. The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther. 1997; 281(2): 855-60.
  64. Narahashi T. Nerve membrane Na+ channels as targets of insecticides. Trends Pharmacol Sci. 1992 Jun; 13(6): 236-41.
  65. Zhao X, Dai S, Chen G. Inhibition of glutamate uptake in rat brain synaptosome by pyrethroids. Chung Hua Yu Fang I Hsueh Tsa Chih. 1995; 29(2): 89-91.
  66. Eldefrawi AT, Eldefrawi ME. Receptors for gamma-aminobutyric acid and voltage-dependent chloride channels as targets for drugs and toxicants. FASEB J. 1987; 1(4): 262-71.
  67. Zuccari Bissacot D, Vassilieff I. HPLC determination of flumethrin, deltamethrin, cypermethrin, and cyhalothrin residues in the milk and blood or lactating dairy cows. Journal of Analytical Toxicology. 1997; 21(5): 397-402.
  68. Gassner B, Wuthrich A, Lis J, Scholtysik G, Solioz M. Topical application of synthetic pyrethroids to cattle as a source of persistent environmental contamination. J Environ Sci Health B. 1997; 32(5): 729.
  69. McGuire, Longstreth, et al. Occupational exposures and amyotrophic lateral sclerosis. J Epidemiol. 1997; 145(12): 1076-88.
  70. Kamel F, Umbach DM, Hu H, Sandler DP. Lead exposure and amyotrophic lateral sclerosis. J Epidemiol. 2002; 13(3): 311-319.
  71. Onradi S, Ronnevi LO, Vesterberg O. Abnormal tissue distribution of lead in amyotrophic lateral sclerosis. J Neurol Sci. 1976; 29(2-4): 259-65.
  72. Fang F, Kwee LC, Allen KD, et al. Association between blood lead and the risk of amyotrophic lateral sclerosis. J Epidemiol. 2010; 171(10): 1126.
  73. Wang H, O’Reilly EJ, Ascherio A, et al. Smoking and risk of amyotrophic lateral sclerosis: A pooled analysis of 5 prospective cohorts. Arch Neurol. 2011 Feb; 68(2): 207-13.
  74. McGuire V, Longstreth WT Jr., van Belle G. Occupational exposures and amyotrophic lateral sclerosis: A population-based case-control study. J Epidemiol. 1997; 145(12): 1076-88.
  75. Nelson LM, McGuire V, Longstreth WT Jr., Matkin C. Population-based case-control study of amyotrophic lateral sclerosis in western Washington state. J Epidemiol. 2000; 151(2): 156-63.
  76. Armon I. An evidence-based medicine approach to the evaluation of the role of exogenous risk factors in sporadic amyotrophic lateral sclerosis. Neuroepidemiology. 2003; 22(4): 217-28.
  77. Sutedja NA, Veldink JH, Fischer K, et al. Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: A systematic review. Amyotrophic Lateral Scler. 2009 Oct-Dec; 10(5-6): 302-9.
  78. Weisskopf MG, Morozova N, et al. Prospective study of chemical exposures and amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2009 May; 80(5): 558-61.
  79. Migliore L, Coppede F. Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res. 2009; 674(1-2): 73-84.
  80. Goldberg AF, et al. Effect of amalgam restorations on whole body potassium and bone mineral content in older men. Gen Dent. 1996; 44(3): 246-8.
  81. Schirrmacher K. Effects of lead, mercury, and methylmercury on gap junctions and [Ca2+]I in bone cells. Calcif Tissue Int. 1998; 63(2): 134-9.
  82. Redhe O, Pleva J. Recovery from ALS and from asthma after removal of dental amalgam fillings. Int J Risk & Safety in Med. 1994; 4: 229-236.
  83. Adams CR, Ziegler DK, Lin JT. Mercury intoxication simulating ALS. JAMA. 1983; 250(5): 642-5.
  84. Seidler A, et al. Possible environmental factors for Parkinson’s disease. Neurology. 1996; 46(5): 1275-1284.
  85. Ohlson, et al. Parkinson’s disease and occupational exposure to mercury. Scand J of Work Environment Health. 1981; 7(4): 252-256.
  86. Quig D. Cysteine metabolism and metal toxicity. Altern Med Rev. 1998; 3(4): 262-270.
  87. de Ceaurriz, et al. Role of gamma- glutamyltraspeptidase(GGC) and extracellular glutathione in dissipation of inorganic mercury. J Appl Toxicol. 1994; 14(3): 201.
  88. Berndt WO, et al. Renal glutathione and mercury uptake. Fundam Appl Toxicol. 1985; 5(5): 832-9.
  89. Zalups RK, Barfuss DW. Accumulation and handling of inorganic mercury in the kidney after co-administration with glutathione. J Toxicol Environ Health. 1995; 44(4): 385-99.
  90. Clarkson TW, et al. Billiary secretion of glutathione-metal complexes. Fundam Appl Toxicol. 1985; 5(5): 816-31.
  91. Aschner M, et al. Metallothionein induction in fetal rat brain by in utero exposure to elemental mercury vapor. Brain Res. 1997; 778(1): 222-32.
  92. Baauweegers HG, Troost D. Localization of metallothionein in the mammilian central nervous system. Biol Signals. 1994; 3: 181-7.
  93. O’Halloran TV. Transition metals in control of gene expression. Science. 1993; 261(5122): 715-25.
  94. Matts RL, Schatz JR, Hurst R, Kagen R. Toxic heavy metal ions inhibit reduction of disulfide bonds. J Biol Chem. 1991; 266(19): 12695-702.
  95. Boot JH. Effects of SH-blocking compounds on the energy metabolism in isolated rat hepatocytes. Cell Struct Funct. 1995; 20(3): 233-8.
  96. Ronnback L, et al. Chronic encephalopaties induced by low doses of mercury or lead. Br J Ind Med. 1992; 49: 233-240.
  97. Langauer H, Lewowicka. Changes in the nervous system due to occupational metallic mercury poisoning. Neurol Neurochir Pol. 1997; 31(5): 905-13.
  98. Kim P, Choi BH. Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes. Yonsei Med J. 1995; 36(3): 299-305.
  99. Brookes N. In vitro evidence for the role of glutatmate in the CNS toxicity of mercury. Toxicology. 1992; 76(3): 245-56.
  100. Albrecht J, Matyja E. Glutamate: A potential mediator of inorganic mercury toxicity. Metab Brain Dis. 1996; 11: 175-84.
  101. Singh I, Pahan K, Khan M, Singh AK. Cytokine-mediated induction of ceramid production is redox-sensitive: Implications to pro-inflammatory cytokine-mediated apoptosis in demyelinating diseases. J Biol Chem. 1998; 273(32): 20354-62.
  102. Pahan K, Raymond JR, Singh I. Inhibition of phosphatidylinositol 3-kinase induces nitric-oxide synthase in lipopolysaccharide- or cytokine-stimulated C6 glial cells. J Biol Chem. 1999; 274: 7528-7536.
  103. Xu J, Yeh CH, et al. Involvement of de novo ceramide biosynthesis in tumor necrosis factor-alpha/cycloheximide-induced cerebral endothelial cell death. J Biol Chem. 1998; 273(26): 16521-6.
  104. Dbaibo GS, El-Assaad W, et al, Ceramide generation by two distinct pathways in tumor necrosis factor alpha-induced cell death. FEBS Lett. 2001; 503(1): 7-12.
  105. Liu B, Hannun YA, et al. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem. 1998; 273(18): 11313-20.
  106. Noda M, Wataha JC, et al. Sublethal, 2-week exposures of dental material components alter TNF-alpha secretion of THP-1 monocytel. Dental Materials. 2003; 19(2): 101-105.
  107. Kim SH, Johnson VJ, Sharma RP. Mercury inhibits nitric oxide production but activates pro-inflammatory cytokine expression in murine macrophage: Differential modulation of NF-kappaB and p38 MAPK signaling pathways. Nitric Oxide. 2002; 7(1): 67-74.
  108. Dastych J, Metcalfe DD, et al. Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-beta-D-hexosaminidase and secrete IL-4 and TNF-alpha. J Allergy Clin Immunol. 1999; 103(6): 1108-14.
  109. Tortarolo M, Veglianese P, et al. Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol Cell Neurosci. 2003; 23(2): 180-92.
  110. Christensen MM, Ellermann-Eriksen S, Mogensen SC. Influence of mercury chloride on resistance to generalized infection with herpes simplex virus type 2 in mice. Toxicology. 1996; 14(1): 57-66.
  111. Ariza ME, Bijur GN, Williams MV. Lead and mercury mutagenesis: Role of H2O2, superoxide dismutase, and xanthine oxidase. Environ Mol Mutagen. 1998; 31(4): 352-61.
  112. Ariza ME, et al. Mercury mutagenisis. Biochem Mol Toxicol. 1999; 13(2): 107-12.
  113. Ariza ME, et al. Mutagenic effect of mercury. InVivo. 1994; 8(4): 559-63.
  114. Gorell JM, et al. Occupational exposure to mercury, manganese, copper, lead, and the risk of Parkinson’s disease. Neurotoxicology. 1999; 20(2-3): 239-47.
  115. Wood M. Mechanisms for the neurotoxicity of mercury. Organotransitional Metal Chemistry. New York: Plenum Publishing Corp; 1987.
  116. Sharma RP, et al. Metals and neurotoxic effects. J of Comp Pathology. 1981; 91.
  117. Monnet-Tschudi F, et al. Comparison of the developmental effects of 2 mercury compounds on glial cells and neurons in the rat telencephalon. Brain Res. 1996; 741: 52-59.
  118. Langworth, et al. Effects of low exposure to inorganic mercury on the human immune system. Scand J Work Environ Health. 1993; 19(6): 405-413.
  119. Walum E, et al. Use of primary cultures to study astrocytic regulatory functions. Clin Exp Pharmoacol Physiol. 1995; 22: 284-7.
  120. Kerkhoff H, Troost D, Louwerse ES. Inflammatory cells in the peripheral nervous system in motor neuron disease. Acta Neuropathol. 1993; 85: 560-5.
  121. Appel Sh, Smith RG. Autoimmunity as an etiological factor in amyotrophic lateral sclerosis. Adv Neurol. 1995; 68: 47-57.
  122. Ngim CH, et al. Epidemiologic study on the association between body burden mercury level and idiopathic Parkinson’s disease. Neuroepidemiology. 1989; 8(3): 128-41.
  123. Larkfors L, et al. Methylmercury induced alterations in the nerve growth factor level in the developing brain. Res Dev Res. 1991; 62(2): 287.
  124. Mathieson PW. Mercury: God of TH2 cells. Clinical Exp Immunol. 1995; 102(2): 229-30.
  125. Heo Y, Parsons PJ, Lawrence DA. Lead differentially modifies cytokine production in Vitaminro and in vivo. Toxicol Appl Pharmacol. 1996; 138: 149-57.
  126. Murdoch RD, Pepys J. Enhancement of antibody and IgE production by mercury and platinum salts. Int Arch Allergy Appl Immunol. 1986 80: 405-11.
  127. Zalups RK, et al. Nephrotoxicity of inorganic mercury co-administered with cysteine. Toxicology. 1996l; 109(1): 15-29.
  128. Capuzzo A. Cd2+ and Hg2+ affect glucose release and cAMP-dependent transduction pathway in isolated eel hepatocytes. Aquat Toxicol. 2003; 62(1): 55-65.
  129. Fabbri E, Caselli F, Piano A, Sartor G, Capuzzo A. Fluctuation of trace elements during methylmercury toxication and chelation therapy. Hum Exp Toxicol. 1994; 13(12): 815-23.
  130. Bapu C, Purohit RC, Sood PP, West ES, et al. Textbook of Biochemistry. MacMillan Co; 1957: 853.
  131. Danielsson BRG, et al. Ferotoxicity of inorganic mercury: distribution and effects of nutrient uptake by placenta and fetus. Biol Res Preg Perinatal. 1984; 5(3):102-109.
  132. Haley B. The toxic effects of mercury on CNS proteins: Similarity to observations in Alzheimer’s disease. IAOMT Symposium paper. 1997.
  133. Pendergrass JC. Mercury vapor inhalation inhibits binding of GTP: Similarity to lesions in Alzheimer diseased brains. Neurotoxicology. 1997; 18: 315.
  134. Palkiewicz P, Zwiers H, Lorscheider FL. ADP & ribosylation of brain neuronal proteins is altered by in vitro and in vivo Exposure to inorganic mercury. Journal of Neurochemistry. 1994; 62(5): 2049, 2052.
  135. Shenker BJ, et al. Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes: Alterations in cell viability. Immunopharmacologicol Immunotoxical. 1992; 14(3): 555-77.
  136. Miller MA, et al. Mercuric chloride induces apoptosis in human lymphocytes. Toxicol Appl Pharmacol. 1998; 153(2): 250, 257.
  137. Rossi AD, Viviani B, Vahter M. Inorganic mercury modifies Ca2+ signals, triggers apoptosis, and potentiates NMDA toxicity in cerebral granule neurons. Cell Death and Differentiation. 1997; 4(4): 317-24.
  138. Goering PL, Thomas D, Rojko JL, Lucas AD. Mercuric chloride-induced apoptosis is dependent on protein synthesis. Toxicol Lett. 1999; 105(3): 183-95.
  139. Defense Against Mystery Syndromes. Davis M, Ed. Chek Printing Co; 1994.
  140. Kantarjian A. A syndrome clinically resembling amyotrophic lateral sclerosis following chronic mercurialism. Neurology. 1961; 11: 639, 644.
  141. Schoeny R. Use of genetic toxicology data in U.S. EPA risk assessment: The mercury study. Environ Health Perspect. 1996; 104(3): 663-73.
  142. Iyer K, et al. Mercury poisoning in a dentist. Arch Neurol. 1976; 33: 788-790.
  143. Sorensen FW, Larsen JO, Eide R, Schionning JD. Neuron loss in cerebellar cortex of rats exposed to mercury vapor: A stereological study. Acta Neuropathol (Berl). 2000; 100(1): 95-100.
  144. Shikata E, Mochizuki Y, Oishi M, Takasu T. A case of chronic inorganic mercury poisoning with progressive intentional tremor and remarkably prolonged latency of P300. Rinsho Shinkeigaku. 1998; 38(12): 1064-6.
  145. Yamanaga H, Quantitative analysis of tremor in Minamata disease. Tokhoku J Exp Med. 1983; 141(1): 13, 22.
  146. Shenker BJ, et al. Immunotoxic effects of mercuric compounds on human lymphoctes and monocytes: Alterations in cellular glutathione content. Immunopharmacol Immunotoxicol. 1993; 15(2-3): 273-90.
  147. al-Saleh I, Shinwari N. Urinary mercury levels in females: Influence of dental amalgam fillings. Biometals. 1997; 10(4): 315-23.
  148. Zabinski Z, Dabrowski Z, Moszczynski P, Rutowski J. The activity of erythrocyte enzymes and basic indices of peripheral blood erythrocytes from worker chronically exposed to mercury vapors. Toxicol Ind Health. 2000; 16(2): 58-64.
  149. Rice DC. Evidence of delayed neurotoxicity produced by methylmercury developmental exposure. Neurotoxicology. 1996; 17(3-4): 583-96.
  150. Weiss B, Clarkson TW, Simon W. Silent latency periods in methylmercury poisoning and in neurodegenerative disease. Environ Health Perspect. 2002; 110(5): 851-4.
  151. Woods JS, et al. Altered porphyrin metabolites as a biomarker of mercury exposure and toxicity. Physiol Pharmocol. 1996; 74(2): 210-15.
  152. Strubelt O, Kremer J, et al. Comparative studies on the toxicity of mercury, cadmium, and copper toward the isolated perfused rat liver. J Toxicol Environ Health. 1996; 47(3): 267-83.
  153. Kaliman PA, Nikitchenko IV, Sokol OA, Strel’chenko EV. Regulation of heme oxygenase activity in rat liver during oxidative stress induced by cobalt chloride and mercury chloride. Biochemistry (Mosc). 2001; 66(1): 77-82.
  154. Kumar SV, Maitra S. Bhattacharya S. In Vitaminro binding of inorganic mercury to the plasma membrane of rat platelet affects Na+-K+-Atpase activity and platelet aggregation. Biometals. 2002; 15(1): 51-7.
  155. Kumar AR, Kurup PA. Inhibition of membrane Na+-K+ ATPase activity: A common pathway in central nervous system disorders. J Assoc Physicians India. 2002; 50: 400-6.
  156. Danielsson BR, et al. Behavioral effects of prenatal metallic mercury inhalation exposure in rats. Neurotoxicol Teratol. 1993; 15(6): 391-6.
  157. Fredriksson A, et al. Prenatal exposure to metallic mercury vapour and methyl-mercury produce interactive behavioral changes in adult rats. Neurotoxicol Teratol. 1996; 18(2): 129-34.
  158. Eggleston DW. Effect of dental amalgam and nickel alloys on T-lympocytes. J Prosthet Dent. 1984; 51(5): 617-623.
  159. Eggleston DW, et al. Correlation of dental amalgam with mercury in brain tissue. J Prosthet Dent. 1987; 58(6): 704-7.
  160. Shenker BJ. Low-level MeHg exposure causes human T-cells to undergo apoptosis: Evidence of mitochondrial dysfunction. Environ Res. 1998; 77(2): 149-159.
  161. Insug O, et al. Mercuric compounds inhibit human monocyte function by inducing apoptosis: Evidence for formation of reactive oxygen species(ROS), development of mitochondrial membrane permeability, and loss of reductive reserve. Toxicology. 1997; 124(3): 211-24.
  162. Warfvinge K. Mercury distribution in the neonatal and adult cerebellum after mercury vapor exposure of pregnant squirrel monkeys. Environ Res. 2000; 83(2): 93-101.
  163. Hisatome I, Kurata Y, et al. Block of sodium channels by divalent mercury: Role of specific cysteinyl residues in the P-loop region. Biophys J. 2000; 79(3): 1336-45.
  164. Bhattacharya S, Sen S, et al. Specific binding of inorganic mercury to Na(+)-K(+)-ATPase in rat liver plasma membrane and signa transduction. Biometals. 1997; 10(3): 157-62.
  165. Anner BM, Moosmayer M, Imesch E. Mercury blocks Na-K-ATPase by a ligand-dependent and reversible mechanism. Am J Physiol. 1992; 262(5.2): 830-6.
  166. Anner BM, Moosmayer M. Mercury inhibits Na-K-ATPase primarily at the cytoplasmic side. Am J Physiol. 1992; 262(5.2): 84308.
  167. Wagner CA, Waldegger S, et al. Heavy metals inhibit Pi-induced currents through human brush-border NaPi-3 cotransporter in Xenopus oocytes. Am J Physiol. 1996 Oct; 271(4.2): 926-30.
  168. Lewis RN, Bowler K. Rat brain Na+-K+ATPase: Modulation of its ouabain & PNPPase activity by thimerosal. Int J Biochem. 1983; 15(1): 5-7.
  169. Rajanna B, Hobson M, Harris L, Ware L, Chetty CS. Effects of cadmium and mercury on Na(+)-K(+) ATPase and uptake of 3H-dopamine in rat brain synaptosomes. Arch Int Physiol Biochem. 1990; 98(5): 291-6.
  170. Hobson M, Rajanna B. Influence of mercury on uptake of dopamine and norepinephrine. Toxicol Letters. 1985; 27: 2-3, 7-14.
  171. McKay SJ, Reynolds JN, Racz WJ. Effects of mercury compounds on the spontaneous and potassium-evoked release of 3H dopamine from mouse striatial slices. Can J Physiol Pharmacol. 1986; 64(12): 1507-14.
  172. Scheuhammer AM, Cherian MG. Effects of heavy metal cations, sulfhydryl reagents and other chemical agents on striatal D2 dopamine receptors. Biochem Pharmacol. 1985; 34(19): 3405-13.
  173. Hoyt KR, et al. Mechanisms of dopamine-induced cell death and differences from glutamate induced cell death. Exp Neurol. 1997; 143(2): 269-81.
  174. Offen D, et al. Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium channels. Neurology. 1998; 51(4): 1100-3.
  175. Huggins HA, Levy TE. Cerebrospinal fluid protein changes in MS after dental amalgam removal. Alternative Med Rev. 1998; 3(4): 295-300.
  176. Bucio L, et al. Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line. Mutat Res. 1999; 423(1-2): 65-72.
  177. Ho PI, Ortiz D, Rogers E, Shea TB. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA. J Neurosci Res. 2002; 70(5): 694-702.
  178. Snyder RD, Lachmann PJ. Thiol involvement in the inhibition of DNA repair by metals in mammalian cells. Source Mol Toxicol. 1989; 2(2): 117-28.
  179. Verschaeve L, et al. Comparative in vitro cytogenetic studies in mercury-exposed human lymphocytes. Muta Res. 1985; 157(2-3): 221-6.
  180. Verschaeve L. Genetic damage induced by level mercury exposure. Envir Res. 2976; 12 306-10.
  181. Soderstrom S, Fredriksson A, Dencker L, Ebendal T. The effect of mercury vapor on cholinergic neurons in the fetal brain. Brain Res. 1995; 85: 96-108.
  182. Abdulla EM, et al. Comparison of neurite outgrowth with neurofilament protein levels in neuroblastoma cells following mercuric oxide exposure. Clin Exp Pharmocol Physiol. 1995; 22(5): 362-3.
  183. Leong CC, Syed NI, Lorscheider FL. Retrograde degeneration of neurite membrane structural integrity of nerve growth cones following in vitro exposure to mercury. Neuroreport. 2001; 12(4): 733-7.
  184. Duhr EF, Pendergrass JC, Slevin JT, Haley BE. HgEDTA complex inhibits GTP interactions with the E & site of brain beta & tubulin. Toxicol App Pharmacol. 1993; 122 (2): 273-80.
  185. Alexianu ME, Kozovska M, Appel SH. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology. 2001; 57(7): 1282-9.
  186. Kubicka-Muranyi M, et al. Systemic autoimmune disease induced by mercuric chloride. Int Arch Allergy Immunol. 1996; 109(1): 11-20.
  187. Warfyinge K, et al. Systemic autoimmunity due to mercury vapor exposure in genetically susceptible mice. Toxicol Appl Pharmacol. 1995; 132(2): 299-309.
  188. Bagenstose LM, et al. Mercury induced autoimmunity in humans. Immunol Res. 1999; 20(1): 67-78.
  189. Engin-Deniz B, et al. Die queckssilberkonzentration im spichel zehnjariger kinder in korrelation zur anzahl und Grobe iher amalgamfullungen. Zeitschrift fur Stomatologie. 1992; 89: 471-179.
  190. Shenker BJ, et al. Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes: Alterations in B-cell function and viability. Immunopharmacol Immunotoxicol. 1993; 15(1): 87-112.
  191. Daum JR. Immunotoxicology of mercury and cadmium o B-lymphocytes. Int J Immunopharmacol. 1993; 15(3): 383-94.
  192. Johansson U, et al. The genotype determines the B cell response in mercury-treated mice. Int Arch Allergy Immunol. 1998; 116(4): 295-305.
  193. Arvidson B. Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motorneurons. Muscle Nerve. 1992; 15(10): 1089-94.
  194. Mitchell JD. Heavy metals and trace elements in amyotrophic lateral sclerosis. Neurol Clin. 1987; 5(1): 43-60.
  195. Su M, et al. Selective involvement of large motor neurons in the spinal cord of rats treated with methylmercury. J Neurol Sci. 1998; 156(1): 12-7.
  196. Danscher G, et al. Localization of mercury in the CNS. Environ Res. 1986; 41: 29-43.
  197. Danscher G, Horsted-Bindslev P, Rungby J. Traces of mercury in organs from primates with amalgam fillings. Exp Mol Pathol. 1990; 52(3): 291-9.
  198. Poulsen EH. Ultrastructural localization of mercury after exposure to mercury vapor. Prog Histochem Cytochem. 1991; 23: 249-255.
  199. Pamphlett R, Coote P. Entry of low doses of mercury vapor into the nervous system. Neurotoxicology. 1998; 19(1): 39-47.
  200. Pamphlett, et al. Oxidative damage to nucleic acids in motor neurons containin Hg. J Neurol Sci. 1998; 159(2): 121-6.
  201. Pamphlett R, Waley P. Motor neuron uptake of low dose inorganic mercury. J Neurol Sci. 1996; 135: 63-67.
  202. Schionning JD, Danscher G. Autometallographic inorganic mercury correlates with degenerative changes in dorsal root ganglia of rats intoxicated with organic mercury. APMIS. 1999; 107(3): 303.
  203. Arvidson B, Arvidsson J, Johansson K. Mercury deposits in neurons of the trigeminal ganglia after insertion of dental amalgam in rats. Biometals. 1994; 7 (3): 261-263.
  204. Arvidson B. Inorganic mercury is transported from muscular nerve terminasl to spinal and brainstem motorneurons. Muscle Nerve. 1992; 15: 1089-94.
  205. Arvidson B, et al. Retograde axonal transport of mercury in primary sensory neurons. Neurosci Letters. 1990; 115: 29-32.
  206. Candura SM et al. Effects of mercuryic chloride and methylmercury on cholinergic neuromusular transmission. Pharmacol Toxicol. 1997; 80(5): 218-24.
  207. Castoldi AF, et al. Interaction of mercury compounds with muscarinic receptor subtypes in the rat brain. Neurotoxicology. 1996; 17(3-4): 735-41.
  208. Wilkinson LJ, Waring RH. Cysteine dioxygenase: modulation of expression in human cell lines by cytokines and control of sulphate production. Toxicol In Vitro. 2002; 16(4): 481-3.
  209. Heafield MT, et al. Plasma cysteine and sulphate levels in patients with Motor neurone disease, Parkinson’s disease, and Alzheimer’s disease. Neurosci Lett. 1990; 110(1-2): 216-220.
  210. Pean A, et al. Pathways of cysteine metabolism in MND/ALS. J Neurol Sci. 1994; 124: 69-61.
  211. Steventon GB, et al. Xenobiotic metabolism in motor neuron disease. Lancet. 1988: 644-47.
  212. Woolsey J. Cysteine, sulfite, and glutamate toxicity: A cause of ALS? Altern Complement Med. 2008; 14(9): 1159-64.
  213. Gordon C, et al. Abnormal sulfur oxidation in systemic lupus erythrmatosus(SLE). Lancet. 1992; 339: 8784, 25-6.
  214. Emory P, et al. Poor sulphoxidation in patients with rheumatoid arthritis. Ann Rheum Dis. 1992; 51(3): 318-20.
  215. Bradley H, et al. Sulfate metabolism is abnormal in patients with rheumatoid arthritis: Confirmation by in vivo biochemical findings. J Rheumatol. 1994; 21(7): 1192-6.
  216. Perry TL, et al. Hallevorden-Spatz Disease: cysteine accumulation and cysteine dioxygenase deficiency. Ann Neural. 1985; 18(4): 482-489.
  217. Freitas AJ, et al. Effects of Hg2+ and CH3Hg+ on Ca2+ fluxes in the rat brain. Brain Res. 1996; 738(2): 257-64.
  218. Yallapragoda PR, et al. Inhibition of calcium transport by Hg salts in rat cerebellum and cerebral cortex. J Appl Toxicol. 1996; 164(4): 325-30.
  219. Chavez E, et al. Mitochondrial calcium release by Hg+2. J Biol Chem. 1988; 263(8): 3582.
  220. Szucs A, et al. Effects of inorganic mercury and methylmercury on the ionic currents of cultured rat hippocampal neurons. Cell Mol Neurobiol. 1997; 17(3): 273-8.
  221. Busselberg D. Calcium channels as target sites of heavy metal. Toxicol Lett. 1995; 82-83: 255-61.
  222. Rossi AD, et al. Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. FASEB J. 1993; 7: 1507-14.
  223. Boadi WY, et al. In vitro effect of mercury on enzyme activities and its accumulation in the first-trimester human placenta. Environ Res. 1992; 57(1): 96-106.
  224. Boadi WY. In vitro exposure to mercury and cadmium alters term human placenta membrane fluidity. Toxicol App Pharmacol. 1992; 116(1): 17-23.
  225. Urbach J, et al. Effect of inorganic mercury on in vitro placental nutrient transfer and oxygen consumption. Reprod Toxicol. 1992; 6(1): 69-75.
  226. Karp W, Gale TF, et al. Effect of mercuric acetate on selected enzymes of maternal and fetal hamsters. Environmental Research. 1985; 36: 351-358.
  227. Karp W, et al. Correlation of human placental enzymatic activity with tracemetal concentration in placenta. Environmental Research. 1977; 13: 470- 477.
  228. Boot JH. Effects of SH-blocking compounds on the energy metabolism and glucose uptake in isolated rat hepatocytes. Cell Struct Funct. 1995 Jun; 20(3): 233-8.
  229. Clauw DJ. The pathogenesis of chronic pain and fatigue syndromes: Fibromyalgia. Med Hypothesis. 1995; 44: 369-78.
  230. Hanson S. Fibromyalgia, glutamate, and mercury. Heavy Metal Bulletin. 1994; 4: 5-6.
  231. Stejskal VDM, Danersund A, Lindvall A. Metal-specific memory lympocytes: Biomarkers of sensitivity in man. Neuroendocrinology Letters. 1999.
  232. Stejskal V, Hudecek R, Mayer W. Metal-specific lymphocytes: Risk factors in CFS and other related diseases. Neuroendocrinology Letters. 1999; 20: 289-298.
  233. Sterzl I, Prochazkova J, Stejskal VDM, et al. Mercury and nickel allergy: Risk factors in fatigue and autoimmunity. Neuroendocrinology Letters. 1999; 20: 221-228.
  234. Prochazkova J, Sterzl I, Kucerova H, Bartova J, Stejskal VD. The beneficial effect of amalgam replacement on health in patients with autoimmunity. Neuroendocrinology Letters. 2004; 25(3): 211-8.
  235. Godfrey ME. Candida, dysbiosis, and amalgam. J Adv Med. 1996; 9(2).
  236. Romani L. Immunity to candida albicans: Th1,Th2 cells and beyond. Curr Opin Microbiol. 1999; 2(4): 363-7.
  237. Stejskal J, Stejskal V. The role of metals in autoimmune diseases and the link to neuroendocrinology. Neuroendocrinology Letters. 1999; 20: 345-358.
  238. Puschel G, Mentlein R, Heymann E. Isolation and characterization of dipeptyl peptidase IV from human placenta. Eur J Biochem. 1982; 126(2): 359-65.
  239. Kar NC, Pearson CM. Dipeptyl peptidases in human muscle disease. Clin Chim Acta. 1978; 82(1-2): 185-92.
  240. Shibuya-Saruta H, Kasahara Y, Hashimoto Y. Human serum dipeptidyl peptidase IV (DPPIV) and its unique properties. J Clin Lab Anal. 1996; 10(6): 435-40.
  241. Blais A, Morvan-Baleynaud J, Friedlander G, Le Grimellec C. Primary culture of rabbit proximal tubules as a cellular model to study nephrotoxicity of xenobiotics. Kidney Int. 1993; 44(1): 13-8.
  242. Moreno-Fuenmayor H, Borjas L, Arrieta A, Valera V. Plasma excitatory amino acids in autism. Invest Clin. 1996; 37(2): 113-28.
  243. Carlsson ML. Is infantile autism a hypoglutamatergic disorder? J Neural Transm. 1998; 105(4-5): 525-35.
  244. Rolf LH, Haarman FY, Grotemeyer KH, Kehrer H. Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand. 1993; 87(5): 312-6.
  245. Naruse H, Hayashi T, Takesada M, Yamazaki K. Metabolic changes in aromatic amino acids and monoamines in infantile autism and a new related treatment. No To Hattatsu. 1989; 21(2): 181-9.
  246. Plaitakis A, Constantakakis E. Altered metabolism of excitatory amino acids, N-acetyl-aspartate and acetyl-aspartyl-glutamate in amyotrophic lateral sclerosis. Brain Res Bull. 1993; 30(3-4): 381-6.
  247. Rothstein JD, Martin LJ, Kuncl RW. Decreased glutamate transport by the brain and spinal cord in ALS. New Engl J Med. 1992; 326: 1464-8.
  248. Leigh PN. Pathologic mechanisms in ALS and other motor neuron diseases. In: Calne DB, ed. Neurodegenerative Diseases. WB Saunder Co; 1997: 473-88.
  249. Froissard P, et al. Role of glutathione metabolism in the glutamate-induced programmed cell death of neuronal cells. Eur J Pharmacol. 1997; 236(1): 93-99.
  250. Zagami CJ, Beart PM, Wallis N, Nagley P, O’Shea RD. Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis. Glia. 2009 Jan 15; 57(2): 119-35.
  251. Kim P, Choi BH. Selective inhibition of glutamate uptake by mercury in cultured mouse astrocytes. Yonsei Med J. 1995; 36(3): 299-305.
  252. Brookes N. In vitro evidence for the role of glutatmate in the CNS toxicity of mercury. Toxicology. 1992; 76(3): 245-56.
  253. Albrecht J, Matyja E. Glutamate: A potential mediator of inorganic mercury toxicity. Metab Brain Dis. 1996; 11: 175-84.
  254. Tirosh O, Sen CK, Roy S, Packer L. Cellular and mitochondrial changes in glutamate-induced HT4 neuronal cell death. Neuroscience. 2000; 97(3): 531-41.
  255. Andreadou E, Vassilopoulos D, et al. Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis. In Vivo. 2008 Jan-Feb; 22(1): 137-41.
  256. Folkers K, et al. Biochemical evidence for a deficiency of vitamin B6 in subjects reacting to MSL-Glutamate. Biochem Biophys Res Comm. 1981; 100: 972.
  257. Felipo V, et al. L-carnatine increases the affinity of glutamate for quisqualate receptors and prevents glutamate neurotoxicity. Neurochemical Research. 1994; 19(3): 373-377.
  258. Akaike A, et al. Protective effects of a Vitamin-B12 analog(methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons. Eur J Pharm. 1993; 241(1): 1-6.
  259. Srikantaiah MV, Radhakrishnan AN. Studies on the metabolism of Vitamin B6 in the small intestine: Purification and properties of monkey intestinal pyridoxal kinase. Indian J Biochem. 1997; 7(3): 151-6.
  260. Barber T. Inorganic mercury intoxification similar to ALS. J of Occup Med. 1978; 20: 667-9.
  261. Brown IA. Chronic mercurialism: A cause of the clinical syndrome of ALS. Arch Neurol Psychiatry. 1954; 72: 674-9.
  262. Schwarz S, Husstedt I. ALS after accidental injection of mercury. J Neurol Neurosurg Psychiatry. 1996; 60: 698.
  263. Felmus MT, Patten BM, Swanke L. Antecedent events in amyotrophic lateral sclerosis. Neurology. 1976 Feb; 26(2): 167-72.
  264. Patten BM, Mallette LE. Motor neuron disease: retrospective study of associated abnormalities. Dis Nerv Syst. 1977 Jun; 37(6): 318-21.
  265. Chetty CS, McBride V, Sands S, Rajanna B. Effects in vitro on rat brain Mg(++)-ATPase. Arch Int Physiol Biochem. 1990; 98(5): 261-7.
  266. Bara M, Guiet-Bara A, Durlach J. Comparison of the effects of taurine and magnesium on electrical characteristics of artificial and natural membranes: Study on the human amnion of the antagonism between magnesium, taurine and polluting metals. Magnesium. 1985; 4(5-6): 325-32.
  267. Carroll RE, Masterton G, Goodwin GM. The neuropsychiatric sequelae of mercury poisoning: The Mad Hatter’s disease revisited. Br J Psychiatry. 1995; 167(1): 95-8.
  268. Fukino H, Hirai M, Hsueh YM, Yamane Y. Effect of zinc pretreatment on mercuric chloride-induced lipid peroxidation in the rat kidney. Toxicol Appl Pharmacol. 1984; 73(3): 395-401.
  269. Estevez AG, Beckman JS, et al. Induction of nitric oxide & dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science. 1999; 286(5449): 2498-500.
  270. Sutton KG, McRory JE, Guthrie H, Snutch TP. P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A. Nature. 1999; 401(6755): 800-4.
  271. Godfrey ME, Wojcik DP, Krone CA. Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity. J Alzheimers Dis. 2003; 5(3): 189-95.
  272. Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006), Northland Environmental Health Clinic. Neuroendocrinology Letters. 2006; 27(4): 415-23.
  273. Mondal MS, Mitra S. Inhibition of bovine xanthine oxidase activity by Hg2+ and other metal ions. J Inorg Biochem. 1996; 62(4): 271-9.
  274. Sastry KV, Gupta PK. In vitro inhibition of digestive enzymes by heavy metals and their reversal by chelating agents. Environ Contam Toxicol. 1978; 20(6): 729-35.
  275. Gupta PK, Sastry KV. Effect of mercuric chloride on enzyme activities in the digestive system and chemical composition of liver and muscles of the catfish. Ecotoxicol Environ Saf. 1981; 5(4): 389-400.
  276. Olanow CW, Arendash GW. Metals and free radicals in neurodegeneration. Curr Opin Neurol. 1994, 7(6): 548-58.
  277. Kasarskis EJ. Metallothionein in ALS Motor Neurons (IRB #91-22026). FEDRIP database. National Technical Information Service. ID: FEDRIP/1999/07802766.
  278. Troy CM, Shelanski ML. Down-regulation of copper/zinc superoxide dismutase causes apototic death in PC12 neuronal cells. Proc. National Acad Sci, USA. 1994; 91(14): 6384-7.
  279. Rothstein JD, Dristol LA, Hosier B, Brown RH, Kunci RW. Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc Nat Acad Sci, USA. 1994; 91(10): 4155-9.
  280. Beal MF. Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases. Biofactors. 199; 9(2-4): 262-6.
  281. DiMauro S, Moses LG. CoQ10 use leads to dramatic improvements in patients with muscular disorders. Neurology. 2001.
  282. Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuro-protective effects. Proc Natl Acad Sci, USA. 1998; 95(15): 8892-7.
  283. Schulz JB, Matthews RT, Henshaw DR, Beal MF. Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: Implications for neurodegenerative diseases. Neuroscience. 1996; 71(4): 1043-8.
  284. Nagano S, Ogawa Y, Yanaghara T, Sakoda S. Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice. Neurosci Lett. 1999; 265(3): 159-62.
  285. Gooch C, et al. Eleanor & Lou Gehrig MDA/ALS Center at Columbia-Presbyterian Medical Center in New York. ALS Newsletter. 2001; 6(3).
  286. Ascherio A, Weisskopf MG, O’reilly EJ. Vitamin E intake and risk of amyotrophic lateral sclerosis. Ann Neurol. 2005; 57(1): 104-10.
  287. Blumer W. Mercury toxicity and dental amalgam fillings. J Adv Med. 1998; 11(3): 219.
  288. Rasmussen HH, Mortensen PB, Jensen IW. Depression and magnesium deficiency. Int J Psychiatry Med. 1989; 19(1): 57-63:
  289. Bekaroglu M, Aslan Y, Gedik Y, Karahan C. Relationships between serum free fatty acids and zinc with ADHD. J Child Psychol Psychiatry. 1996; 37(2): 225-7.
  290. Maes M, Vandoolaeghe E, Neels H, et al. Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biol Psychiatry. 1997; 42(5): 349-358.
  291. Olivieri G, Brack C, Muller-Spahn F, et al. Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tauphosphorylation in SHSY5Y neuroblastoma cells. J Neurochem. 2000 Jan; 74(1): 231-6.
  292. Tabner BJ, Turnbull S, El-Agnaf OM, Allsop D. Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer’s disease and Parkinson’s disease. Free Radic Biol Med. 2002; 32(11): 1076-83.
  293. Ho PI, Collins SC, et al. Homocysteine potentiates beta-amyloid neurotoxicity: Role of oxidative stress. J Neurochem. 2001; 78(2): 249-53.
  294. Johnson S. The possible role of gradual accumulation of copper, cadmium, lead and iron and depletion of zinc, magnesium, selenium, Vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis. Med Hypotheses. 2000; 55(3): 239-41.
  295. White AR, Cappai R. Neurotoxicity from glutathione depletion is dependent on extracellular trace copper. J Neurosci Res. 2003; 71(6): 889-97.
  296. van Benschoten MM. Acupoint energetics of mercury toxicity and amalgam removal with case studies. American Journal of Acupuncture. 1994; 22(3): 251-262.
  297. Nicolson G, Nasralla M, Haier J, Pomfret J. High frequency of systemic mycoplasmal infections in Gulf War veterans and civilians with Amyotrophic Lateral Sclerosis (ALS). J Clin Neurosci. 2002; 9(5): 525.
  298. Umanekii KG, Dekonenko EP. Structure of progressive forms of tick-borne encephalitis. Zh Nevropatol Psikhiatr Im S S Korsakova. 1983; 83(8): 1173-9.
  299. B Hemmer, F X Glocker, R Kaiser. Generalised motor neuron disease as an unusual manifestation of borrelia burgdorferi infection. J Neurol Neurosurg Psychiatry. 1997; 63: 257-258.
  300. Fredrikson S, Link H. CNS-borreliosis selectively affecting central motor neurons. Acta Neurol Scand. 1988; 78: 181-184.
  301. Halperin JJ, Kaplan GP, Brazinsky S, et al. Immunologic reactivity against borrelia burgdorferi in patients with motor neuron disease. Arch Neurol. 1990; 47: 586-594.
  302. Landner L, Lindestrom L. Copper in Society and the Environment. 2nd ed. Swedish Environmental Research Group (MFG); 1999.
  303. White AR, Cappai R, Neurotoxicity from glutathione depletion is dependent on extracellular trace copper. J Neurosci Res. 2003; 71(6): 889-97.
  304. Waggoner DJ, Bartnikas TB, Gitlin JD. The role of copper in neurodegenerative disease. Neurobiol Dis. 1999; 6(4): 221-30.
  305. Torsdottir G, Kristinsson J, Gudmundsson G, Snaedal J, Johannesson T. Copper, ceruloplasmin and superoxide dismutase (SOD) in amyotrophic lateral sclerosis. Pharmacol Toxicol. 2000; 87(3): 126-30.
  306. Estevez AG, Beckman JS, et al. Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science. 1999; 286(5449): 2498-500.
  307. Cookson MR, Shaw PJ. Oxidative stress and motor neurons disease. Brain Pathol. 1999; 9(1): 165-86.
  308. Shibata N, Nagai R, Kobayashi M. Morphological evidence for lipid peroxidation and protein glycoxidation in spinal cords from sporadic amyotrophic lateral sclerosis patients. Brain Res. 2001; 917(1): 97-104.
  309. Cookson MR, Shaw PJ. Oxidative stress and motor neurons disease. Brain Pathol. 1999; 9(1): 165-86.
  310. Kobayashi MS, Han D, Packer L. Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity. Free Radic Res. 2000; 32(2): 115-24.
  311. Ferrante RJ, Klein AM, Dedeoglu A, Beal MF. Therapeutic efficacy of EGb761 (Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis. J Mol Neurosci. 2001; 17(1): 89-96.
  312. Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med. 1997; 22(1-2): 359-78.
  313. Li Y, Liu L, et al. Vitamin E suppression of microglial activation is neuro-protective. J Neurosci Res. 2001; 66(2): 163-70.
  314. Kang JH, Eum WS. Enhanced oxidative damage by the familial amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutants. Biochem Biophys Acta. 2000; 1524(2-3): 162-70.
  315. Eum WS. Enhanced oxidative damage by the familial amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutants. Biochem Biophys Acta. 2000; 1524(2-3): 162-70.
  316. Liu H, Zhu H, Eggers DK, Nersissian AM, et al. Copper(2+) binding to the surface residue cysteine 111 of His46Arg human copper & zinc superoxide dismutase, a familial amyotrophic lateral sclerosis mutant. Biochem. 2000; 39(28): 8125-32.
  317. Wong PC, Gitlin JD, et al. Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. Proc Natl Acad Sci, USA. 2000; 97(6): 2886-91.
  318. Kruman II, Pedersen WA, Springer JE, Mattson MP. ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis. Exp Neurol. 1999; 160(1): 28-39.
  319. Doble A. The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol Ther. 1999; 81(3): 163-221.
  320. Urushitani M, Shimohama S. N-methyl-D-aspartate receptor-mediated mitochondrial Ca(2+) overload in acute excitotoxic motor neuron death: a mechanism distinct from chronic neurotoxicity after Ca(2+) influx. J Neurosci Res. 2001; 63(5): 377-87.
  321. Cookson MR, Shaw PJ. Oxidative stress and motor neurons disease. Brain Pathol. 1999; 9(1): 165-86.
  322. Torres-Aleman I, Barrios V, Berciano J. The peripheral insulin-like growth factor system in amyotrophic lateral sclerosis and in multiple sclerosis. Neurology. 1998; 50(3): 772-6.
  323. Dall R, Sonksen PH, et al. The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. 2000 Study Group. J Clin Endocrinol Metab. 2000; 85(11): 4193-200.
  324. Pons S, Torres-Aleman I. Insulin-like growth factor-I stimulates dephosphorylation of ikappa B through the serine phosphatase calcineurin. J Biol Chem. 2000; 275(49): 38620-5.
  325. Lai EC, Rudnicki SA. Effect of recombinant human insulin-like growth factor—Ion progression of ALS. A placebo-controlled study. Neurology. 1997; 49(6): 1621-30.
  326. Yuen EC, Mobley WC. Therapeutic applications of neurotrophic factors in disorders of motor neurons and peripheral nerves. Mol Med Today. 1995; 1(6): 278-86.
  327. Dore S, Kar S, Quirion R. Rediscovering an old friend, IGF-I: Potential use in the treatment of neurodegenerative diseases. Trends Neurosci. 1997; 20(8): 326-31.
  328. Couratier P, Vallat JM. Therapeutic effects of neurotrophic factors in ALS. Rev Neurol. 2000; 156(12): 1075-7.
  329. Van den Berghe G, Bowers C, et al. Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin releasing hormone and its combination with growth hormone secretagogues. J Clin Endocrinol Metab. 1998; 83(2): 309-19.
  330. Vielhaber S, Kaufmann J, Kunz WS. Effect of creatine supplementation on metabolite levels in ALS motor cortices. Exp Neurol. 2001; 172(2): 377-82.
  331. Andreassen OA, Jenkins BG, Dedeoglu A, Ferrante KL, Beal MF. Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem. 2001; 77(2): 383-90.
  332. Friedlander, R et al. Combination of creatine and minocycline increase survival rate synergistically. Annals of Neurology. 2003.
  333. Leistevuo J, Pyy L, Osterblad M. Dental amalgam fillings and the amount of organic mercury in human saliva. Caries Res. 2001; 35(3): 163-6.
  334. Appel SH, Beers D, Siklos L, Engelhardt JI, Mosier DR. Calcium: The Darth Vader of ALS. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001; 2(1): 47-54.
  335. Niebroj-Dobosz I, Jamrozik Z, Janik P, Hausmanowa-Petrusewicz I, Kwiecinski H. Anti-neural antibodies in serum and cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients. Acta Neurol Scand. 1999; 100(4): 238-43.
  336. Appel SH, Stockton-Appel V, Stewart SS, Kerman RH. Amyotrophic lateral sclerosis. Associated clinical disorders and immunological evaluations. Arch Neurol. 1986; 43(3): 234-8.
  337. Pestronk A, Choksi R. Multifocal motor neuropathy: Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates. Neurology. 1997; 49(5): 1289-92.
  338. Pestronk A, Adams RN, Cornblath D, Kuncl RW, Drachman DB, Clawson L. Patterns of serum IgM antibodies to GM1 and GD1a gangliosides in amyotrophic lateral sclerosis. Ann Neurol. 1989; 25(1): 98-102.
  339. Earl C, Chantry A, Mohammad N. Zinc ions stabilize the association of basic protein with brain myelin membranes. J Neurochem. 1988; 51: 718-24.
  340. Riccio P, Giovanneli S, Bobba A. Specificity of zinc binding to myelin basic protein. Neurochem Res. 1995; 20: 1107-13.
  341. Sanders B. The role of general and metal-specific cellular responses in protection and repair of metal-induced damage: stress proteins and metallothioneins. In: Chang L, ed. Toxicology of Metals. Lewis Publishers, CRC Press Inc.; 1996: 835-52.
  342. Mendez-Alvarez E, Soto-Otero R, et al. Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson’s disease. Biochim Biophys Acta. 2002; 1586(2): 155-68.
  343. Yasui M, Yase Y, Ota K, Garruto RM. Aluminum deposition in the central nervous system of patients with amyotrophic lateral sclerosis from the Kii Peninsula of Japan. Neurotoxicology. 1991; 12(3): 61-20.
  344. Garruto RM, Swyt C, Fiori CE, Yanagihara R, Gajdusek DC. Intraneuronal deposition of calcium and aluminium in amyotropic lateral sclerosis of Guam. Lancet. 1985; 2(8468): 1353.
  345. Garruto RM, Shankar SK, Yanagihara R, Salazar AM, Amyx HL, Gajdusek DC. Low-calcium, high-aluminum diet-induced motor neuron pathology in cynomolgus monkeys. Acta Neuropathol. 1989; 78(2): 210-9.
  346. Oyanagi K, Kawakami E, Yasui M, et al. Magnesium deficiency over generations in rats with special references to the pathogenesis of the Parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Neuropathology. 2006; 26(2): 115-28.
  347. Yasui M, Yoshida M, Tamaki T, Taniguchi Y, Ota K. Similarities in calcium and magnesium metabolism between amyotrophic lateral sclerosis and calcification of the spinal cord in the Kii Peninsula ALS focus. No To Shinkei. 1997; 49(8): 745-51.
  348. Wakayama I, Nerurkar VR, Strong MJ, Garruto RM. Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis. Acta Neuropathol. 1996; 92(6): 545-54.
  349. Kong J, Xu Z. Mitochondrial degeneration in motor neurons triggers the onset of ALS in mice expressing a mutant SOD1 gene. J Neurosci. 1998; 18: 3241-50.
  350. Cassarino DS, Bennett JPJ. Mitochrondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res Brain Res Rev. 1999; 29: 1-25.
  351. Mitchell JD. Heavy metals and trace elements in amyotrophic lateral sclerosis. Neurol Clin. 1987; 5(1): 43-60.
  352. Sienko DG, Davis JP, Taylor JA. ALS: A case-control study following detection of a cluster in a small Wisconsin community. Arch Neurol. 1990; 9: 255-62.
  353. Provinciali L, Giovagnoli A. Antecedent events in ALS: Do they influence clinical onset and progression? Neuroepidemiology. 1990; 9: 255-62.
  354. Roelofs-Iverson RA, Elveback LR. ALS and heavy metals. Neurology. 1984; 34: 393-5.
  355. ArmonC, O’Brien PC. Epidemiologic correlates of sporadic ALS. Neurology. 1991; 41: 1077-84.
  356. Vanacore N, Corsi L, Fabrizio E, Bonifati V, Meco G. Relationship between exposure to environmental toxins and motor neuron disease: A case report. Med Lav. 1995; 86(6): 522-33.
  357. Yase Y. Environmental contribution to the ALS process. In: Serratrice G, ed. Neuromuscular Diseases. New York: Raven Press; 1984: 335-9.
  358. Guermonprez L, Ducrocq C, Gaudry-Talarmain YM. Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants. Mol Pharmacol. 2001; 60(4): 838-46.
  359. Mahboob M, Shireen KF, Atkinson A, Khan AT. Lipid peroxidation and antioxidant enzyme activity in different organs of mice exposed to low level of mercury. J Environ Sci Health B. 2001; 36(5): 687-97.
  360. Miyamoto K, Nakanishi H, et al. Involvement of enhanced sensitivity of N-methyl-D-aspartate receptors in vulnerability of developing cortical neurons to methylmercury neurotoxicity. Brain Res. 2001; 901(1-2): 252-8.
  361. Anuradha B, Varalakshmi P. Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation. Pharmacol Res. 1999; 39(1): 67-80.
  362. Kawashima T, Doh-ura K, Iwaki T. Cognitive dysfunction in patients with amyotrophic lateral sclerosis is associated with spherical or crescent-shaped ubiquitinated intraneuronal inclusions in the parahippocampal gyrus and amygdala, but not in the neostriatum. Acta Neuropathol (Berl). 2001; 102(5): 467-72.
  363. Urushitani M, Shimohama S. The role of nitric oxide in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001; 2(2): 71-81.
  364. Torreilles F, Salman-Tabcheh S, Guerin M, Torreilles J. Neurodegenerative disorders: The role of peroxynitrite. Brain Res. 1999; 30(2): 153-63.
  365. Aoyama K, Matsubara K, Kobayashi S. Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann Neurol. 2000; 47(4): 524-7.
  366. Guermonprez L, Ducrocq C, Gaudry-Talarmain YM. Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants. Mol Pharmacol. 2001; 60(4): 838-46.
  367. Ahlbom II, Cardis E, Green A, Linet M, SaVitaminz D, Swerdlow A. Review of the Epidemiologic Literature on EMF and Health. Environ Health Perspect. 2001; 109 (6): 911-933.
  368. Beuter A, de Geoffroy A, Edwards R. Quantitative analysis of rapid pointing movements in Cree subjects exposed to mercury and in subjects with neurological deficits. Environ Res. 1999; 80(1): 50-63.
  369. Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med. 1997; 22(1-2): 359-78.
  370. McCarty MF. Versatile cytoprotective activity of lipoic acid may reflect its ability to activate signaling intermediates that trigger the heat-shock and phase II responses. Med Hypotheses. 2001; 57(3): 313-7.
  371. Whiteman M, Tritschler H, Halliwell B. Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by oxidized and reduced lipoic acid. FEBS Lett. 1996; 379(1): 74-6.
  372. Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002; 7(6): 456-71.
  373. Gregus Z, et al. Effect of lipoic acid on biliary excretion of glutathione and metals. Toxicol Appl Pharmacol. 1992, 114(1): 88-96.
  374. Mutter J, et al. Alzheimer disease: Mercury as pathogenetic factor and apolipoprotein E as a moderator. Neuroendocrinol Lett. 2004; 25(5): 331-339.
  375. Cave S, Mitchell D. What Your Doctor May Not Tell You About Children’s Vaccinations. Warner Books; 2001.
  376. Waly, M. et al. Activation of methionine synthase by insulin-like growth factor-1 and dopamine: A target for neurodevelopmental toxins and thimerosal. 2004: 1-13.
  377. Haley, B. Mercury and thimerosal toxicity: A factor in autism. Proc Natl Acad Sci, USA. 2008; 105: 2052-2057.
  378. Feng HL, Leng Y, Ma CH, Zhang J, Ren M, Chuang DM. Combined lithium and valproate treatment delays disease onset, reduces neurological deficits, and prolongs survival in an amyotrophic lateral sclerosis mouse model. Neuroscience. 2008; 155(3): 567-72.
  379. Should depressive syndromes be reclassified as “Metabolic Syndrome Type II”? Ann Clin Psychiatry. 2007; 19(4): 257-64.
  380. McIntyre RS, Soczynska JK, Kennedy SH et al. Inflammation, depression and dementia: Are they connected? Neurochem Res. 2007; 32(10): 1749-56.
  381. Blaylock, RL. Immunoexcitotoxicity. Alt Ther Health Med. 2008; 14: 46-53.
  382. Rayssiguier Y, Gueux E, et al. High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. Magnes Res. 2006; 19(4): 237-43.
  383. Bo S. Dietary magnesium and fiber intakes and inflammatory and metabolic indicators in middle-aged subjects from a population-based cohort. Am J Clin Nutr. 2006; 84(5): 1062-9.
  384. Guerrero-Romero F, Rodriguez-More. Hypomagnesemia, oxidative stress, inflammation, and metabolic syndrome. Diabetes Metab Res Rev. 2006; 22(6): 471-6.
  385. Guerrero-Romero F, Rodriguez-More. Effects of antidiabetic and antihyperlipidemic agents on C-reactive protein. Mayo Clin Proc. 2008; 83(3): 333-42.
  386. Vasdev S, Gill V, Singal P. Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications. Cell Biochem Biophys. 2007; 49(1): 48-63.
  387. Barnes DM, Kircher EA; & Effects of inorganic HgCl2 on adipogenesis. Toxicol Sci. 2003; 75(2): 368-77.
  388. Barnes DM, Hanlon PR, Kircher EA. Heavy metal-induced inhibition of active transport in the rat small intestine in vitro: Interaction with other ions. Comp Biochem Physiol C. 1986; 84(2): 363-8.
  389. Iturri SJ, Penta A. Interaction of the sugar carrier of intestinal brush-border membranes with HgCl2. Biochim Biophys Acta. 1980; 598(1): 100-14.
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