突触内外NMDA受体的分布调控及其生物学功能

神经药理学报››2011,Vol. 1››Issue (5): 40-48.

突触内外NMDA受体的分布调控及其生物学功能

楚世峰，陈乃宏

天然药物活性物质与功能国家重点实验室,中国医学科学院,药物研究所,北京,100050,中国

出版日期:2011-10-26发布日期:2013-03-24
通讯作者:陈乃宏，男，教授，博士生导师；研究方向：神经药理及神经分子生物学；Tel:+86-010-63165177, Fax:+86-010-63165211，E-mail: chennh@imm.ac.cn
作者简介:楚世峰，男，博士研究生；研究方向：神经药理及神经分子生物学；E-mail: chushifeng@imm.ac.cn
基金资助:

国家自然科学基金（No.30801527、30973887、U832008、90713045、81072541），科技部项目（No.2010DFB32900），创新药物重大专项（No.2012ZX09301002-004）

Distinct Roles and Modulations of Synaptic and Extrasynaptic NMDA Receptors

CHU Shi-feng, CHEN Nai-hong

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica ,Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050,China

Online:2011-10-26Published:2013-03-24
Contact:陈乃宏，男，教授，博士生导师；研究方向：神经药理及神经分子生物学；Tel:+86-010-63165177, Fax:+86-010-63165211，E-mail: chennh@imm.ac.cn
About author:楚世峰，男，博士研究生；研究方向：神经药理及神经分子生物学；E-mail: chushifeng@imm.ac.cn
Supported by:

国家自然科学基金（No.30801527、30973887、U832008、90713045、81072541），科技部项目（No.2010DFB32900），创新药物重大专项（No.2012ZX09301002-004）

摘要/Abstract

摘要：N-甲基-D-天冬氨酸受体(N-Methyl-D-Aspartate receptor，NMDA受体)历来被认为是一把双刃剑。一方面，它可介导钙离子内流，增强突触可塑性，提高神经元兴奋性；另一方面，它的过度开放导致钙离子过量内流，形成钙超载，引起细胞功能紊乱，诱发凋亡，或启动细胞死亡信号转导途径。然而，最近的研究表明NMDA受体的生物学效应并不完全取决于其开放程度，不同部位的NMDA受体可激活不同的信号转导通路，产生相反的生物学效应。其中突触上的NMDA受体活化可通过作用于细胞核内的钙离子信号转导通路，发挥保护神经细胞的作用；而突触外的NMDA受体则可诱发细胞的凋亡甚至死亡途径。两者之间的失衡是神经系统疾病发病的主要机制之一，例如在老年痴呆以及亨廷顿氏病中，均发现有NMDA受体分布的异常。因此，调控NMDA受体的分布为神经退行性疾病的治疗提供一个新的方向。

关键词:NMDA受体,突触,突触外,凋亡,信号转导

Abstract:N-Methyl-D-Aspartate receptor（NMDA receptor） has been considered as a double-edged sword in central nervous system. On the one hand, it mediates the calcium influx, promotes the synaptic plasticity and improves the neural excitatory. On the other hand, excessive opening of NMDA receptor causes calcium overload in neurons, disturbing the homeostasis and inducing the apoptosis. However, growing number of studies demonstrated that the distinct roles of NMDA receptor do not totally depend on its opening degree, but also on its locations where different signaling pathways are triggered. Synaptic NMDA receptors activate the nuclear calcium signaling pathways to protect the neurons; whereas activation of extrasyanptic NMDA receptor starts the apoptosis or death pathway. The imbalance between the two pathways accounts partially for pathogenesis in neural diseases, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. In conclusion, the currently available evidence has provided a new clue for the treatment of neurodegenerative disease.

Key words:NMDA receptor,synaptic,extrasynaptic,apoptosis,signaling pathway

中图分类号:

R964

楚世峰，陈乃宏. 突触内外NMDA受体的分布调控及其生物学功能[J]. 神经药理学报, 2011, 1(5): 40-48.

CHU Shi-feng, CHEN Nai-hong. Distinct Roles and Modulations of Synaptic and Extrasynaptic NMDA Receptors[J]. Acta Neuropharmacologica, 2011, 1(5): 40-48.

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