The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-ß and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations.
Int J Mol Sci
; 25(3)2024 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-38338914
ABSTRACT
Alzheimer's disease and Type 2 diabetes are two epidemiologically linked diseases which are closely associated with the misfolding and aggregation of amyloid proteins amyloid-ß (Aß) and human islet amyloid polypeptide (hIAPP), respectively. The co-aggregation of the two amyloid proteins is regarded as the fundamental molecular mechanism underlying their pathological association. The green tea extract epigallocatechin-3-gallate (EGCG) has been extensively demonstrated to inhibit the amyloid aggregation of Aß and hIAPP proteins. However, its potential role in amyloid co-aggregation has not been thoroughly investigated. In this study, we employed the enhanced-sampling replica exchange molecular dynamics simulation (REMD) method to investigate the effect of EGCG on the co-aggregation of Aß and hIAPP. We found that EGCG molecules substantially diminish the ß-sheet structures within the amyloid core regions of Aß and hIAPP in their co-aggregates. Through hydrogen-bond, π-π and cation-π interactions targeting polar and aromatic residues of Aß and hIAPP, EGCG effectively attenuates both inter-chain and intra-chain interactions within the co-aggregates. All these findings indicated that EGCG can effectively inhibit the co-aggregation of Aß and hIAPP. Our study expands the potential applications of EGCG as an anti-amyloidosis agent and provides therapeutic options for the pathological association of amyloid misfolding disorders.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catequina
/
Diabetes Mellitus Tipo 2
/
Polipeptídeo Amiloide das Ilhotas Pancreáticas
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2024
Tipo de documento:
Article