Polyphenol-solubility Alters Amyloid Fibril Formation of α-synuclein

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2021 May 28

PMID 34046949

Citations 7

Authors

Masatomo So

Yuto Kimura

Keiichi Yamaguchi

Toshihiko Sugiki

Toshimichi Fujiwara

Cesar Aguirre

Kensuke Ikenaka

Hideki Mochizuki

Yasushi Kawata

Yuji Goto

Affiliations

Soon will be listed here.

Abstract

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Amyloid fibrils form above the solubility of amyloidogenic proteins or peptides upon breaking supersaturation, followed by a nucleation and elongation mechanism, which is similar to the crystallization of solutes. Many additives, including salts, detergents, and natural compounds, promote or inhibit amyloid formation. However, the underlying mechanisms of the opposing effects are unclear. We examined the effects of two polyphenols, that is, epigallocatechin gallate (EGCG) and kaempferol-7─O─glycoside (KG), with high and low solubilities, respectively, on the amyloid formation of α-synuclein (αSN). EGCG and KG inhibited and promoted amyloid formation of αSN, respectively, when monitored by thioflavin T (ThT) fluorescence or transmission electron microscopy (TEM). Nuclear magnetic resonance (NMR) analysis revealed that, although interactions of αSN with soluble EGCG increased the solubility of αSN, thus inhibiting amyloid formation, interactions of αSN with insoluble KG reduced the solubility of αSN, thereby promoting amyloid formation. Our study suggests that opposing effects of polyphenols on amyloid formation of proteins and peptides can be interpreted based on the solubility of polyphenols.

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