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Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils

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...

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Autores principales: Tavanti, Francesco, Pedone, Alfonso, Menziani, Maria Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100107/
https://www.ncbi.nlm.nih.gov/pubmed/29857500
http://dx.doi.org/10.3390/molecules23061320
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author Tavanti, Francesco
Pedone, Alfonso
Menziani, Maria Cristina
author_facet Tavanti, Francesco
Pedone, Alfonso
Menziani, Maria Cristina
author_sort Tavanti, Francesco
collection PubMed
description 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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spelling pubmed-61001072018-11-13 Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils Tavanti, Francesco Pedone, Alfonso Menziani, Maria Cristina Molecules Article 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. MDPI 2018-05-31 /pmc/articles/PMC6100107/ /pubmed/29857500 http://dx.doi.org/10.3390/molecules23061320 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tavanti, Francesco
Pedone, Alfonso
Menziani, Maria Cristina
Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
title Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
title_full Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
title_fullStr Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
title_full_unstemmed Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
title_short Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1–40) Fibrils
title_sort computational insight into the effect of natural compounds on the destabilization of preformed amyloid-β(1–40) fibrils
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100107/
https://www.ncbi.nlm.nih.gov/pubmed/29857500
http://dx.doi.org/10.3390/molecules23061320
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