Table 1Neurodegenerative diseases thought to be mediated at least in part through stimulation of glutamate receptors

Huntington's disease (pathologic process mimicked by injection of the endogenous NMDA agonist quinolinate; mitochondrial inhibitors, which make neurons more susceptible to glutamate toxicity, can reproduce this process)
AIDS dementia complex (human immunodeficiency virus-associated cognitive-motor complex) (evidence that neuronal loss is ameliorated by NMDA antagonists in vitro and in animal models)
Neuropathic pain syndromes (e.g., causalgia or painful peripheral neuropathies with a central component blocked by NMDA-receptor antagonists or inhibitors of nitric oxide synthase)
Olivopontocerebellar atrophy (some recessive forms associated with glutamate dehydrogenase deficiency)
Parkinsonism (mimicked by impaired mitochondrial metabolism, which renders neurons more susceptible to glutamate-induced toxicity)
Amyotrophic lateral sclerosis (primary defect may be a mutation in superoxide dismutase gene, which may render motor neurons more vulnerable to glutamate-induced toxicity; there is also evidence for decreased glutamate reuptake)
Mitochondrial abnormalities and other inherited or acquired biochemical disorders (partial listing)
MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes due to a point mutation in mitochondrial DNA)
MERRF (myoclonus epilepsy with ragged-red fibers, signifying mitochondrial DNA mutation; also frequently accompanied by ataxia, weakness, dementia, and hearing loss)
Leber's disease (point mutation in mitochondrial DNA, presenting with delayed-onset optic neuropathy and occasionally degeneration of basal ganglia, with dystonia, dysarthria, ataxia, tremors, and decreased vibratory and position sense)
Wernicke's encephalopathy (thiamine deficiency)
Rett syndrome (disease of young girls, presenting with seizures, dementia, autism, stereotypical hand wringing, and gait disorder)
Hyperhomocysteinemia and homocysteinuria (L-homocysteine has been shown to be a weak NMDA-like agonist as is L-homocysteic acid)
Hyperprolinemia (L-proline is a weak NMDA-like agonist)
Nonketotic hyperglycinemia (a case report of some improvement after treatment with an NMDA antagonist)
Hydroxybutyric aminoaciduria
Sulfite oxidase deficiency
Combined systems disease (vitamin B12 deficiency, which may result in accumulation of homocysteine)
Lead encephalopathy
Alzheimer's disease (data that the vulnerability of neurons to glutamate can be increased by β-amyloid protein)
Hepatic encephalopathy (perhaps a component, although inhibitory neurotransmitters are more clearly involved)
Tourette's syndrome (deficits in basal ganglia have been proposed to be mediated by glutamate or glutamate-like toxins)
Drug addiction, tolerance, and dependency (animal modes suggest that NMDA antagonists may be helpful in treatment)
Multiple sclerosis

From: Excitatory Amino Acid Neurotoxicity

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