囊泡谷氨酸转运体在阿尔兹海默病发病机制中的作用  

VGLUTs in the pathogenesis of Alzheimer's disease

作　　者：户东梅[1,2] 程肖蕊[1] 周文霞[1] 张永祥[1] 周立春[2] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]首都医科大学附属北京朝阳医院,北京100043

出　　处：《生命科学》2013年第11期1077-1083,共7页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(30600760;30973541);神经变性病教育部重点实验室开放课题(2013SJBX01)

摘　　要：阿尔兹海默病(Alzheimer's disease,AD)是一种多因素复杂性神经退行性疾病,β淀粉样蛋白(βamyloid,Aβ)级联假说和谷氨酸兴奋性毒性是其重要的发病机制。囊泡谷氨酸转运体(vesicular glutamate transporters,VGLUTs)可特异性地将神经元内的谷氨酸转移入突触囊泡,且一个独立功能单位的VGLUT对于完成一个囊泡的填充是必要和充分的,没有VGLUT的突触囊泡中就没有谷氨酸(glutamate,Glu),VGLUT在一定程度上决定了释放进突触间隙Glu的量,是谷氨酸能突触传递的关键因子。在AD中Aβ增多聚集,VGLUTs表达减低,且VGLUTs转运Glu和Glu的囊泡释放与淀粉样前体蛋白(amyloid precursor protein,APP)代谢和Aβ的释放在突触囊泡的循环中存在的行为平行性和共定位。胞外Aβ的增加可增强囊泡的释放几率,而Glu引起的突触活性增加亦可增加胞外Aβ的浓度。APP/Aβ与谷氨酸能系统之间相互影响导致AD的发生,VGLUTs可能在其中发挥重要作用,被认为是治疗AD的潜在的药物靶点和预警标志物。Alzheimer＇s disease （AD） is a classic multi-factorial complex neurodegenerative disease. The β amyloid （Aβ） toxicol cascade and glutamate excitotoxicity are of the important pathogenesis of AD. Vesicular glutamate transporters （VGLUTs） can specifically transfer glutamate into the synaptic vesicle. One single functional unit of VGLUT is necessary and sufficient to fill successfully vesicle, and the vesicles without VGLUT are empty. VGLUT determines the amount of glutamate that released into the synaptic cleft in some extent and is the key factor of glutamatergic synaptic transmission. There are extensive deposition of Aβ and reduced expression of VGLUT in the brain of AD patients. The processes of vesicle glutamate release and glutamate transferred by VGLUT are parallel with the Aβ release and amyloid precursor protein （APP） metabolism in the synaptic vesicle cycle. VGLUTs co-localize with APP in synaptic vesicle. The increase in extracellular Aβ enhances the probability of vesicle Glu release, and otherwise the increase in glutamate-induced synaptic activity elevates the extracellular concentration of Aβ. The interaction between APP/Aβ and glutamatergic system induced AD, in which VGLUTs may play an important role. VGLUTs have been considered a potential drug target in the treatment of AD and biomarkers in the early diagnosis of AD.

关 键 词：阿尔兹海默病 谷氨酸能神经传递 囊泡谷氨酸转运体 p淀粉样蛋白前体蛋白 D淀粉样蛋白 

分 类 号：R741[医药卫生—神经病学与精神病学] R338.13[医药卫生—临床医学]