神经性疾病相关的谷氨酸转运体研究进展

Glutamate Transporters Involved in Disorders of Central Nervous System

摘要:

谷氨酸是哺乳动物中枢神经系统中最重要的神经递质之一。谷氨酸转运体可分为兴奋性氨基酸转运体(excitatory amino acid transporters, EAATs),即高亲和力转运体和囊泡谷氨酸转运体(vesicular glutamate transporters, VGLUTs),即低亲和力转运体2种类型。其中,EAATs为维持正常的兴奋性突触的转运及受体激活所必需,人类已发现有5个胞浆膜谷氨酸转运体亚型(EAAT1-EAAT5);VGLUTs 的功能是特异地将突触囊泡外的谷氨酸转运至突触囊泡内,主要由3个成员组成,分别为VGLUT1,VGLUT2 和VGLUT3。近年研究发现:很多神经系统疾病都伴随着谷氨酸转运体功能的异常,且其病理特征与谷氨酸转运体亚型、分布、结构以及功能相关。有报道认为,中药中某些成分如麝香酮抗脑缺血损伤与其调节谷氨酸转运体有关。

Abstract:

Glutamate transporters play a key role in the central nervous system(CNS). Glutamate transporters comprise of excitatory amino acid transporters(EAATs) and vesicular glutamate transporters(VGLUTs).In addition to their fundamental role in mediating neurotransmitter uptake, EAATs may contribute to the modulation of a variety of cellular processes. Activation of the excitatory amino acid (EAA) carriers generates an electrogenic current attibutable to ion-coupled cotransport. Structurally distinct subtypes of human glutamate transporters, EAAT1-EAAT5 (1, 2, 11), have been identified and characterized by molecular cloning. VGLUTs transport specifically glutamates into synaptic vesicles in the presynaptic terminal for further release into the synaptic cleft. VGLUT1, VGLUT2 and VGLUT3 are three subtypes of VGLUTs. Recent studies show that many central nervous system disorders are accompanied by abnormal functions of glutamate transporters and the pathological characteristics of the disease are closely related to the particular subtypes, distribution, structures and functions of the glutamate transporters.