Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh, City, Vietnam.
Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam.
Curr Pharm Des. 2018;24(28):3341-3346. doi: 10.2174/1381612824666180813093420.
In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development has been carefully assessed to treat Alzheimer's disease. Aβ peptides can transform structurally from random coil monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the identification of binding targets has been challenging due to the heterogeneity and metastable nature. A better understanding of Aβ species' assembly details and structural properties has been more characterized recently. Numerous potential inhibitors have been identified that they can effectively bind to different Aβ species such as monomer, oligomer or protofibril during the inhibition of Aβ aggregation process. This review highlights the diversity of structural ensembles of Aβ species, from monomer to protofibril forms and the specific binding targets by their potential inhibitors. Comprehending the binding mechanism of Aβ inhibitors is indispensable for searching novel drug candidates against early-stage Alzheimer's disease.
近年来，Aβ 聚集的预防已成为药物开发中最受关注的策略之一，以治疗阿尔茨海默病。Aβ 肽可以从无规卷曲的单体结构转变成β-折叠的原纤维，通过多种寡聚状态。在各种 Aβ 物种中，由于异质性和亚稳态性质，鉴定结合靶标一直具有挑战性。最近，人们对 Aβ 物种的组装细节和结构特性有了更好的理解。已经确定了许多潜在的抑制剂，它们可以在 Aβ 聚集过程中有效地结合不同的 Aβ 物种，如单体、寡聚体或原纤维。本综述强调了 Aβ 物种从单体到原纤维形式的结构多样性，以及它们潜在抑制剂的特定结合靶标。理解 Aβ 抑制剂的结合机制对于寻找针对早期阿尔茨海默病的新型药物候选物是必不可少的。
