Excitatory amino acids and neurotoxicity.
In the past three decades evidence indicating a role for excitatory amino acids in determining certain neurological disorders has been accumulated. Although the mechanisms underlying the neuronal damage induced by glutamate are not yet fully understood, many intracellular processes are thought to contribute to the development of excitotoxic injury, acting in combination to determine cell death. In this article we report the leading hypotheses in the understanding of excitatory amino acid-induced toxicity, which focus on the role of Ca2+ and Ca(2+)-activated processes, for example the activation of Ca(2+)-dependent enzymes such as kinases, lipases and proteases and the formation of the messenger molecule nitric oxide for the production of free radicals, in the development of neuronal damage. The possible implications for excitotoxicity of second messenger systems generated by glutamate acting on the metabotropic receptor subtypes will also be discussed.
Bruno
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V
Institute of Pharmacology, School of Medicine, University of Catania, Italy.
Scapagnini
U
U
Canonico
P L
PL
D001921:Brain / Q000187:drug effects*; D002120:Calcium Channel Agonists / Q000378:metabolism; D016923:Cell Death; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005971:Glutamates / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D009474:Neurons / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism
D002120:Calcium Channel Agonists; D017869:Cyclic GMP-Dependent Protein Kinases; D005609:Free Radicals; D005971:Glutamates; D011493:Protein Kinase C; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate