Understanding the Binding Mechanism of Amyloid-β Inhibitors from Molecular Simulations.

Abstract:

: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.

journal_name

Curr Pharm Des

authors

Tran L

doi

10.2174/1381612824666180813093420

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

3341-3346

issue

28

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-92340

journal_volume

24

pub_type

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