L-CYSTEINE, A BICARBONATE-SENSITIVE ENDOGENOUS EXCITOTOXIN
L-CYSTEINE, A BICARBONATE-SENSITIVE ENDOGENOUS EXCITOTOXIN
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DOI：
10.1126/science.2185543
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发表时间：
1990-05-04
期刊：
影响因子：
56.9
通讯作者：
LABRUYERE, J
中科院分区：
文献类型：
--
作者：
OLNEY, JW;ZORUMSKI, C;LABRUYERE, J
在对未成熟的啮齿类动物全身给药后，L-半胱氨酸破坏大脑皮层、海马、丘脑和纹状体中的神经元，但其潜在机制从未阐明。L-半胱氨酸的这种体外或体内神经毒性现已显示主要通过谷氨酸受体的N-甲基-D-谷氨酸酯亚型介导（在较高浓度下有使君子酸酯受体参与）。此外，在生理浓度的碳酸氢根离子的存在下，L-半胱氨酸的兴奋性毒性效力显著增加。L-半胱氨酸天然存在于人脑和环境中，并且比β-半胱氨酸强得多。N-甲氨基-L-丙氨酸，一种碳酸氢盐依赖性兴奋毒素，与关岛特有的成人神经退行性疾病有关。因此，这种常见的含硫氨基酸在影响中枢神经系统的神经退行性过程中的潜在参与值得考虑。
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-asparate 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.