MECHANISMS OF EXCITOTOXICITY IN NEUROLOGIC DISEASES
MECHANISMS OF EXCITOTOXICITY IN NEUROLOGIC DISEASES
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DOI：
10.1096/fasebj.6.15.1464368
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发表时间：
1992-12-01
期刊：
影响因子：
4.8
通讯作者：
BEAL, MF
中科院分区：
文献类型：
--
作者：
BEAL, MF
兴奋性毒性是指兴奋性氨基酸受体激活引起的神经细胞死亡。大量证据表明兴奋性毒性是急性和慢性神经系统疾病中细胞死亡的一种机制。最近的一个重大进展是成功地克隆和表达了N-甲基-D-天冬氨酸(NMDA)、非NMDA和代谢性谷氨酸受体。这些受体激活后导致细胞死亡的细胞机制仍在阐明中。在急性神经系统疾病中，如中风和头部创伤，兴奋性毒性可能与谷氨酸过度释放有关。然而，在慢性神经退行性疾病中，由于受体异常或能量代谢障碍，更有可能发生缓慢的兴奋毒性过程。最近的治疗研究已经证明了非NMDA受体拮抗剂在全脑缺血的实验研究中的有效性。
Excitotoxicity refers to neuronal cell death caused by activation of excitatory amino acid receptors. A substantial body of-evidence has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurologic diseases. A major recent advance has been the successful cloning and expression of the N-methyl-D-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors. The cellular mechanisms responsible for cell death after activation of these receptors are still being clarified. In acute neurologic diseases such as stroke and head trauma, excitotoxicity may be related to excessive glutamate release. In chronic neurodegenerative diseases, however, a slow excitotoxic process is more likely to occur as a consequence of either a receptor abnormality or an impairment of energy metabolism. Recent therapeutic studies have demonstrated the efficacy of non-NMDA receptor antagonists in experimental studies of global ischemia.