兴奋性氨基酸转运体2在神经退行性变中的作用  

Role of EAAT2 in Neurodegenerative Diseases

作　　者：许保磊[1] 王蓉[1] 

机构地区：[1]首都医科大学宣武医院中心实验室,北京老年病医疗研究中心,神经变性病教育部重点实验室

出　　处：《中国比较医学杂志》2012年第10期67-71,共5页Chinese Journal of Comparative Medicine

基　　金：北京市自然科学基金(编号:7082043);首都卫生发展科研专项项目(编号:2011-1001-02);北京市卫生系统高层次卫生技术人才计划资助项目(编号:2009-3-64)

摘　　要：谷氨酸是脑内必需的兴奋性神经递质之一,兴奋性氨基酸转运体(Excitatory amino acid transporterEAAT)2是最主要的谷氨酸转运体,负责脑内90%以上的谷氨酸再摄取,调节突触间隙的谷氨酸浓度。EAAT2功能紊乱导致胞外谷氨酸过量积聚,在多种神经退行性疾病的发病过程中起重要作用,如阿尔茨海默病、亨廷顿舞蹈病、肌萎缩侧索硬化等。对于人EAAT2启动子的研究发现,NF-kB在星形胶质细胞中对EAAT2表达起关键作用。通过筛选1 040种FDA批准的化合物,发现多种β-内酰胺类抗生素如头孢曲松钠等是EAAT2的转录激活剂,可以增加EAAT2的蛋白表达水平,产生神经保护作用。Glutamate is an essential excitatory neurotransmitter regulating brain functions.Excitatory amino acid transporter（EAAT）-2 is one of the major glutamate transporters expressed predominantly in astroglial cells and is responsible for 90% of total glutamate uptake.Glutamate transporters tightly regulate glutamate concentration in the synaptic cleft.Dysfunction of EAAT2 and accumulation of excessive extracellular glutamate has been implicated in the development of several neurodegenerative diseases including Alzheimer＇s disease,Huntington＇s disease,and amyotrophic lateral sclerosis.Analysis of the human EAAT2 promoter showed that NF-kB is an important regulator of EAAT2 expression in astrocytes.Screening of approximately 1,040 FDA-approved compounds led to the discovery that many b-lactam antibiotics such as ceftriaxone etc.are transcriptional activators of EAAT2 resulting in increased EAAT2 protein levels and produce neuroprotective effects.

关 键 词：谷氨酸 兴奋性氨基酸转运体2 神经退行性变 NF-KB 头孢曲松钠 

分 类 号：R33[医药卫生—人体生理学]