L-cysteine, a bicarbonate-sensitive endogenous excitotoxin

John W. Olney, Charles Zorumski, Madelon T. Price, Joann Labruyere

Research output: Contribution to journalArticle

224 Scopus citations

Abstract

After systemic administration to immature rodents, L-cysteine destroys neurons in the cerebral cortex, hippocampus, thalamus, and striatum, but the underlying mechanism has never been clarified. This neurotoxicity of L-cysteine, in vitro or in vivo, has now been shown to be mediated primarily through the N-methyl-D-aspartate subtype of glutamate receptor (with quisqualate receptor participation at higher concentrations). In addition, the excitotoxic potency of L-cysteine was substantially increased in the presence of physiological concentrations of bicarbonate ion. L-Cysteine is naturally present in the human brain and in the environment, and is much more powerful than β-N-methylamino-L-alanine, a bicarbonate-dependent excitotoxin, which has been implicated in an adult neurodegenerative disorder endemic to Guam. Thus, the potential involvement of this common sulfur-containing amino acid in neurodegenerative processes affecting the central nervous system warrants consideration.

Original languageEnglish
Pages (from-to)596-599
Number of pages4
JournalScience
Volume248
Issue number4955
DOIs
StatePublished - Jan 1 1990

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