Glutamate dysfunction and selective motor neuron degeneration in amyotrophic lateral sclerosis: a hypothesis.
Recent studies provided evidence for a generalized defect in glutamate metabolism in patients with amyotrophic lateral sclerosis, associated with widespread alterations in the central nervous system levels of this excitatory amino acid putative transmitter. Present data support the hypothesis that altered presynaptic glutamatergic mechanisms may be responsible for a neuroexcitotoxic cell loss in this disorder. High local concentrations of glycine, released from glycinergic terminals, may disrupt adaptive processes contributing to abnormal potentiation of excitatory transmission mediated by glutamate receptors and resultant selective degeneration of motor neurons. These considerations offer new therapeutic strategies for amyotrophic lateral sclerosis.
Plaitakis
A
A
Mount Sinai School of Medicine, New York, NY 10029.
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D005969:Glutamate Dehydrogenase; D005998:Glycine