Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, Italy
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Academic Editors: Rebecca Wade and Outi Salo-Ahen
Molecules 2018, 23(6), 1320; https://doi.org/10.3390/molecules23061320
Received: 11 May 2018 / Revised: 28 May 2018 / Accepted: 29 May 2018 / Published: 31 May 2018
(This article belongs to the Special Issue Molecular Modeling in Drug Design)
One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists of either blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-epigallocatechin-3-gallate, quercetin, and rosmarinic acid) with amyloid-β(1–40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulates the double-layered structure stability.
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Keywords:
molecular dynamics simulation; biophenols; natural compounds; amyloid fibrils; Alzheimer’s disease; ligand–protofiber interactions
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Tavanti, F.; Pedone, A.; Menziani, M.C. Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils. Molecules 2018, 23, 1320.
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