阿尔采末病(AD)是一种进行性的神经退行性疾病,其发病原因是脑内β淀粉样蛋白(Aβ)的聚集和沉积。Aβ是由淀粉样蛋白前体经β-分泌酶和γ-分泌酶剪切代谢生成,而β-淀粉样蛋白前体蛋白裂解酶1(BACE1)是该过程的限速酶,抑制BACE1的活性可减少Aβ的产生,因此BACE1成为人们关注治疗AD的热门靶点。本文对近年来BACE1靶点在阿尔采末病治疗中的研究和进展进行综述。
Alzheimer disease (AD) is a progressive neurodegenerative disease, and the pathogenic mechanism involves the accumulation and deposition of the amyloid-beta peptide (Aβ) in brain tissues. Aβ, the product of the large type1 trans-membrane protein amyloid precursor protein (APP), is generated in a two- step proteolytic process by β-secretase and followed by β-secretase. As a β-secretase, β-site anayloid precursor protein-cleaving enzyme 1 (BACE1) is the rate-limiting enzyme of this process. Due to limiting its activity can prevent Aβ generation in AD, BACE1 has become an attractive therapeutic target for the treatment of AD. This review summarized the recent research and development of intervention strategies of BACE1 in AD.