含GluN2A和GluN2B的N-甲基-D-天冬氨酸受体在神经元存活与死亡中的不同作用
Differential roles of GluN2A- and GluN2B-containing NMDA receptors in neuronal survival and death.
作者信息
Lujan Brendan, Liu Xiaoxuan, Wan Qi
机构信息
Department of Physiology and Cell Biology, University of Nevada School of Medicine 1664 North Virginia Street, MS0352, Reno, NV 89557, USA.
出版信息
Int J Physiol Pathophysiol Pharmacol. 2012;4(4):211-8. Epub 2012 Dec 26.
Abstract
Glutamate-induced neurotoxicity is the primary molecular mechanism that induces neuronal death in a variety of pathologies in central nervous system (CNS). Toxicity signals are relayed from extracellular space to the cytoplasm by N-methyl-D-aspartate receptors (NMDARs) and regulate a variety of survival and death signaling. Differential subunit combinations of NMDARs confer neuroprotection or trigger neuronal death pathways depending on the subunit arrangements of NMDARs and its localization on the cell membrane. It is well-known that GluN2B-contaning NMDARs (GluN2BRs) preferentially link to signaling cascades involved in CNS injury promoting neuronal death and neurodegeneration. Conversely, less well-known mechanisms of neuronal survival signaling are associated with GluN2A-comtaining NMDARs (GluN2AR)-dependent signal pathways. This review will discuss the most recent signaling cascades associated with GluN2ARs and GluN2BRs.
摘要
谷氨酸诱导的神经毒性是中枢神经系统（CNS）多种病理状态下诱导神经元死亡的主要分子机制。毒性信号通过N-甲基-D-天冬氨酸受体（NMDARs）从细胞外空间传递到细胞质，并调节各种生存和死亡信号。NMDARs不同的亚基组合根据其在细胞膜上的亚基排列及其定位赋予神经保护作用或触发神经元死亡途径。众所周知，含GluN2B的NMDARs（GluN2BRs）优先与参与CNS损伤的信号级联相连，促进神经元死亡和神经退行性变。相反，与含GluN2A的NMDARs（GluN2AR）依赖性信号通路相关的神经元存活信号机制则鲜为人知。本综述将讨论与GluN2ARs和GluN2BRs相关的最新信号级联。
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