突触外NMDA受体在神经疾病病理机制中的作用 精灵论文.doc

突触外 NMDA 受体在神经疾病病理机制中 的作用 琚珏刚，李胜天 （上海交通大学生命科学技术学院，上海 200240） 5 摘要：N-甲基-D-天门冬氨酸受体（N-methyl-D-aspartate receptor，NMDA 受体，NMDA receptor）是一种主要的离子型谷氨酸受体，而且在中枢神经系统（central nervous system, CNS）的生理与病理过程中都起着重要的作用。正是由于 NMDA 受体的不同亚基组成导致了其 多样性，使其得以在不同条件下行使不同的功能。此外，近期有文献表明突触内（synaptic） 和突触外（extrasynaptic）的 NMDA 受体有着不同的组成以及下游信号通路：突触内 NMDA 10 受体偏向于促进神经元存活而突触外的 NMDA 受体则会促细胞死亡。当前，不少研究都致力 于探明突触外 NMDA 受体在病理过程中的作用，从而希望为相关神经疾病的治疗提供有效的 靶点。在这篇综述中，我们主要回顾了突触内、外 NMDA 受体在病理过程，包括脑缺血、精 神分裂症、抑郁症、癫痫等之中的作用的近期研究进展。 关键词：神经科学；N-甲基-D-天门冬氨酸受体；突触外受体；神经疾病 15 中图分类号：Q180 Psychological Roles of Extrasynaptic NMDA Receptors in Neurologic Diseases JU Juegang, LI Shengtian 20 (School of Life Science and Biotechnology, Shanghai Jiao Tong University, ShangHai 200240) Abstract: The N-methyl-D-aspartate (NMDA) receptor is a major type of ionotropic glutamate receptor, and many studies have shown that it plays a pivotal role in the central nervous system (CNS) under both physiological and pathological conditions. The diversity of NMDA receptor can be mainly attributed to the composition of different subunits that perform multiple functions under various 25 situations. Furthermore, recent reports have indicated that synaptic and extrasynaptic NMDA receptors have distinct compositions and are responsible for different signaling pathways: synaptic NMDA receptors promote cell survival while extrasynaptic NMDA receptors promote cell death. Currently, intensive efforts are being made to study the patholotical role of extrasynaptic NMDA receptors in order to search for a more effective target in the treatment of neurologic disorders. Here we review 30 some recent progress on the participation of synaptic and extrasynaptic NMDA receptors in neurologic diseases including ischemia, schizophrenia, depression and so forth. Keywords:Neuroscience; N-methyl-D-aspartate receptor; extrasynaptic receptor; neurologic disease 0 引言 35 谷氨酸是神经系统中重要的兴奋性递质，谷氨酸受体可分为离子型和代谢型两大类，离 子型谷氨酸受 体又包括 主要通透 Na+ 的 α- 氨 基羟甲基恶