β分泌酶生物学特性的研究进展  

Biological characteristics of β-secretase:research advances

作　　者：王健辉[1] 程肖蕊[1] 周文霞[1] 张永祥[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《国际药学研究杂志》2014年第4期400-406,423,共8页Journal of International Pharmaceutical Research

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09301003-002-001);国家科技支撑计划资助项目(2012BAI29B07);国家自然科学基金资助项目(90709012;30772562;30973541);国家重点基础研究发展计划(973计划)资助项目(2004CB518907)

摘　　要：β分泌酶是一种Ⅰ型跨膜蛋白,其在脑内的主要作用是从Met596和Asp597之间以及Tyr606和Glu607之间切割β淀粉样蛋白前体蛋白(β-amyloid precursor protein,APP)形成β淀粉样蛋白(β-amyloid protein,Aβ)的N端,以启动Aβ生成。β分泌酶包括多个成员,其中因天冬氨酸蛋白酶β-位淀粉样蛋白前体蛋白裂解酶1(β-site amyloid precursor protein-cleaving enzyme 1,BACE1)在阿尔茨海默病(Alzheimer′sdisease,AD)的发病机制中占有重要地位而研究较多。本文主要对BACE1的基因和蛋白结构、转录和翻译调控、胞内运输和调控、代谢及其调控、底物以及与其同源的酶进行综述,为以BACE1为靶点的药物研发提供借鉴。β-secretase, a typeⅠtransmembrane aspartic protease, initiates β-amyloid protein（Aβ） formation by cleaving β-amyloid precursor protein between Met596 and Asp597 or between Tyr606 and Glu607 to generate N-terminal fragment of Aβ. β-Secretase has many members,and aspartic proteinaseβ-site amyloid precursor protein-cleaving enzyme 1 （BACE1） is the most famous of them. Because BACE1 plays a significant role in the pathogenesis of Alzheimer′s disease （AD） and a neurodegenerative disease, it has been studied fully. In this article, we review the gene and protein structure, transcription and translation, intracellular trafficking and metabolism of BACE1 and summarize substrates and homologous enzymes of BACE1. This work provides some reference for BACE1 as a drug target on AD.

关 键 词：Β分泌酶 β淀粉样蛋白前体蛋白裂解酶1 阿尔茨海默病 

分 类 号：R96[医药卫生—药理学]