Inhibition of BACE1 for therapeutic usein Alzheimer's disease

International Journal of Clinical and Experimental Pathology

Xiaoyang Luo¹ 

关键词: Alzheimer's disease;    amyloid plaques;    BACE1;    aspartyl protease;    drug discovery;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Since BACE1 was reported as the β-secretase in Alzheimer's disease (AD) over ten years ago, encouraging progress has been made toward understanding the cellular functions of BACE1. Genetic studies have further confirmed that BACE1 is essential for processing amyloid precursor protein (APP) at the β-secretase site. Only after this cleavage can the membrane-bound APP C-terminal fragment be subsequently cleaved by γ-secretase to release so-called AD-causing Aβ peptides. Hence, in the past decade, a wide variety of BACE1 inhibitors have been developed for AD therapy. This review will summarize the major historical events during the evolution of BACE1 inhibitors designed through different strategies of drug discovery. Although BACE1 inhibitors are expected to be safe in general, careful titration of drug dosage to avoid undesirable side effects in BACE1-directed AD therapy is also emphasized.

【 授权许可】

CC BY-NC