CAJ | 학술논문

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′s disease，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。
β분비매시일충Ⅰ형과막단백，기재뇌내적주요작용시종Met596화Asp597지간이급Tyr606화Glu607지간절할β정분양단백전체단백（β-amyloid precursor protein，APP）형성β정분양단백（β-amyloid protein，Aβ）적N단，이계동Aβ생성。β분비매포괄다개성원，기중인천동안산단백매β-위정분양단백전체단백렬해매1（β-site amyloid precursor protein-cleaving enzyme 1， BACE1）재아이자해묵병（Alzheimer′s disease，AD）적발병궤제중점유중요지위이연구교다。본문주요대BACE1적기인화단백결구、전록화번역조공、포내운수화조공、대사급기조공、저물이급여기동원적매진행종술，위이BACE1위파점적약물연발제공차감。
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.