The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations

Li, Xuhua; Zhang, Yu; Yang, Zhiwei; Zhang, Shengli; Zhang, Lei

doi:10.3390/ijms25031636

Open AccessArticle

The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations

by

Xuhua Li

^1,2,*,†

,

Yu Zhang

^1,†,

Zhiwei Yang

¹

,

Shengli Zhang

¹

and

Lei Zhang

¹

MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi’an Jiaotong University, Xi’an 710049, China

²

State Key Laboratory of Surface Physics, Department of Physics, Fudan University, 2005 Songhu Road, Shanghai 200438, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(3), 1636; https://doi.org/10.3390/ijms25031636

Submission received: 4 January 2024 / Revised: 21 January 2024 / Accepted: 22 January 2024 / Published: 29 January 2024

(This article belongs to the Special Issue Molecular Insights into Macromolecules Structure, Function, and Regulation: 2nd Edition)

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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-β (Aβ) 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 Aβ 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 Aβ and hIAPP. We found that EGCG molecules substantially diminish the β-sheet structures within the amyloid core regions of Aβ and hIAPP in their co-aggregates. Through hydrogen-bond, π–π and cation–π interactions targeting polar and aromatic residues of Aβ 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 Aβ 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.

Keywords: co-aggregation; epigallocatechin-3-gallate; replica exchange molecular dynamics simulation; amyloid-β; human islet amyloid polypeptide

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MDPI and ACS Style

Li, X.; Zhang, Y.; Yang, Z.; Zhang, S.; Zhang, L. The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations. Int. J. Mol. Sci. 2024, 25, 1636. https://doi.org/10.3390/ijms25031636

AMA Style

Li X, Zhang Y, Yang Z, Zhang S, Zhang L. The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations. International Journal of Molecular Sciences. 2024; 25(3):1636. https://doi.org/10.3390/ijms25031636

Chicago/Turabian Style

Li, Xuhua, Yu Zhang, Zhiwei Yang, Shengli Zhang, and Lei Zhang. 2024. "The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations" International Journal of Molecular Sciences 25, no. 3: 1636. https://doi.org/10.3390/ijms25031636

APA Style

Li, X., Zhang, Y., Yang, Z., Zhang, S., & Zhang, L. (2024). The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations. International Journal of Molecular Sciences, 25(3), 1636. https://doi.org/10.3390/ijms25031636

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The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations

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