NMDA受体与中枢神经系统退行性疾病

兴奋性氨基酸（excitatory amino acids, EAA）是存在于中枢神经系统的兴奋性神经递质，主要包括谷氨酸和天门冬氨酸。谷氨酸受体可分为离子型和代谢型两类。N-甲基-D-天冬氨酸（N-Methyl-D-Aspartate, NMDA）受体是离子型受体的一种亚型。NMDA受体可介导Ca2+内流，增强突触可塑性，参与学习记忆及神经系统发育。另一方面，机体兴奋性氨基酸剧增时，通过激动NMDA受体引起大量的Ca2+内流，细胞内Ca2+超载，进一步激活一系列胞内机制而导致细胞死亡。所以NMDA受体历来被认为是一把双刃剑。NMDA受体活性调节的失衡可能是神经退行性疾病、癫痫及缺血性脑损伤等许多中枢神经系统疾病发病的基础。本文重点就NMDA受体与神经退行性疾病的关系进行综述。

NMDA Receptor and Neurodegenerative Diseases in the Central Nervous System

Excitatory amino acids (EAA) are excitatory neurotransmitters in the central nervous system that mainly includes glutamic acid and asparaginic acid. There are two categories of glutamic acid receptors: ionic receptors and metabolic receptors. N-Methyl-D-Aspartate (NMDA) receptor is a subtype of ionic receptors. NMDA receptor mediates the calcium influx, promotes the synaptic plasticity, and participates in process of learning, memory and neurogenesis. On the other hand, excessive excitatory amino acids can excite NMDA receptor, and causes calcium influx, intracellular calciumoverload, further activates a series of intracellular mechanisms inducing the apoptosis. So NMDA receptor has been considered as a double-edged sword in central nervous system. The disturbance of activation regulation of NMDA receptors could be the basis of a plenty of central nervous system diseases including neurodegenerative diseases, epilepsy, ischemic cerebral injury, etc. This article reviews the relationship between NMDA receptors and neurodegenerative diseases.