L-cysteine, a bicarbonate-sensitive endogenous excitotoxin.
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.
Washington University School of Medicine, Department of Psychiatry, St. Louis, MO 63110.
J W
JW
Olney
C
C
Zorumski
M T
MT
Price
J
J
Labruyere
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology*; D002642:Chick Embryo; D003545:Cysteine / Q000494:pharmacology / Q000633:toxicity*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D016202:N-Methylaspartate; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000166:cytology / Q000187:drug effects; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology
D000927:Anticonvulsants; D001639:Bicarbonates; D003986:Dibenzocycloheptenes; D009498:Neurotoxins; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015032:Zinc; D003545:Cysteine