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Science 4 May 1990:
Vol. 248. no. 4955, pp. 596 - 599
DOI: 10.1126/science.2185543
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Articles

Science, Vol 248, Issue 4955, 596-599
Copyright © 1990 by American Association for the Advancement of Science

articles

L-cysteine, a bicarbonate-sensitive endogenous excitotoxin

JW Olney, C Zorumski, MT Price, and J Labruyere

Washington University School of Medicine, Department of Psychiatry, St. Louis, MO 63110.

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 beta-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.


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