Evin Genevieve, Lessene Guillaume, Wilkins Simon
Department of Pathology, and Mental Health Research institute, The University of Melbourne, Parkville VIC, Australia.
Recent Pat CNS Drug Discov. 2011 May 1;6(2):91-106. doi: 10.2174/157488911795933938.
Current drug development for the treatment of Alzheimer's Disease is principally based on the amyloid cascade theory, and aims to reduce the levels of Aβ amyloid peptide in the brain. This can be achieved, either by decreasing peptide production through inhibition of β-secretase (also known as BACE-1) or γ-secretase, or by interfering with Aβ aggregation, or by promoting Aβ clearance. Targeting BACE-1, the proteolytic enzyme that initiates Aβ formation, has generated a lot of research interest recently and is currently thought to be one of the most promising therapeutic approaches. In this review, we summarize and discuss the latest patents and publications describing BACE-1 inhibitors, principally focussing on their drug properties and performance in preclinical trials.
目前用于治疗阿尔茨海默病的药物研发主要基于淀粉样蛋白级联反应理论，旨在降低大脑中Aβ淀粉样肽的水平。这可以通过抑制β-分泌酶（也称为BACE-1）或γ-分泌酶来减少肽的产生，或者通过干扰Aβ聚集，或者通过促进Aβ清除来实现。靶向启动Aβ形成的蛋白水解酶BACE-1，最近引起了很多研究兴趣，目前被认为是最有前途的治疗方法之一。在这篇综述中，我们总结并讨论了描述BACE-1抑制剂的最新专利和出版物，主要关注它们的药物特性和在临床试验前的表现。
