近年来基于 BACE-1 抑制及其他 AD 致病因子的抗阿尔茨海默病药物的设计与开发研究。
Recent Studies on Design and Development of Drugs Against Alzheimer's Disease (AD) Based on Inhibition of BACE-1 and Other AD-causative Agents.
机构信息
Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut-250005, India.
Computer Aided Drug Design Lab, Department of Pharmaceutical Chemistry, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad-201206, Uttar Pradesh, India.
出版信息
Curr Top Med Chem. 2020;20(13):1195-1213. doi: 10.2174/1568026620666200416091623.
BACKGROUND
Alzheimer's disease (AD) is one of the neurodegenerative diseases and has been hypothesized to be a protein misfolding disease. In the generation of AD, β-secretase, γ-secretase, and tau protein play an important role. A literature search reflects ever increasing interest in the design and development of anti-AD drugs targeting β-secretase, γ-secretase, and tau protein.
OBJECTIVE
The objective is to explore the structural aspects and role of β-secretase, γ-secretase, and tau protein in AD and the efforts made to exploit them for the design of effective anti-AD drugs.
METHODS
The manuscript covers the recent studies on design and development of anti-AD drugs exploiting amyloid and cholinergic hypotheses.
RESULTS
Based on amyloid and cholinergic hypotheses, effective anti-AD drugs have been searched out in which non-peptidic BACE1 inhibitors have been most prominent.
CONCLUSION
Further exploitation of the structural aspects and the inhibition mechanism for β-secretase, γ-secretase, and tau protein and the use of cholinergic hypothesis may lead still more potent anti-AD drugs.
背景
阿尔茨海默病（AD）是一种神经退行性疾病，据推测是一种蛋白质错误折叠疾病。在 AD 的发生发展过程中，β-分泌酶、γ-分泌酶和 tau 蛋白起着重要作用。文献检索反映出人们对针对β-分泌酶、γ-分泌酶和 tau 蛋白设计和开发抗 AD 药物的兴趣日益浓厚。
目的
旨在探讨β-分泌酶、γ-分泌酶和 tau 蛋白在 AD 中的结构方面和作用，以及为设计有效的抗 AD 药物而对其进行开发的努力。
方法
本文涵盖了利用淀粉样蛋白和胆碱能假说设计和开发抗 AD 药物的最新研究。
结果
基于淀粉样蛋白和胆碱能假说，已经发现了有效的抗 AD 药物，其中非肽类 BACE1 抑制剂最为突出。
结论
进一步开发β-分泌酶、γ-分泌酶和 tau 蛋白的结构方面和抑制机制，并利用胆碱能假说，可能会产生更有效的抗 AD 药物。
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