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.

中文翻译：

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基于抑制BACE-1和其他AD致病因子的抗阿尔茨海默氏病（AD）药物的设计和开发的最新研究。

背景技术阿尔茨海默氏病（AD）是神经退行性疾病之一，并且已经假设是蛋白质错误折叠疾病。在AD的产生中，β-分泌酶，γ-分泌酶和tau蛋白起重要作用。文献检索反映出人们对设计和开发针对β-分泌酶，γ-分泌酶和tau蛋白的抗AD药物的兴趣与日俱增。目的探讨β-分泌酶，γ-分泌酶和tau蛋白在AD中的结构特征和作用，并努力开发它们以设计有效的抗AD药物。方法该手稿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，在非肽类BACE1抑制剂最为突出的地方，已经找到了有效的抗AD药物。结论进一步开发β-分泌酶，γ-分泌酶和tau蛋白的结构和抑制机制以及胆碱能假说的使用可能会导致更有效的抗AD药物。