1. Polyphenol-solubility alters amyloid fibril formation of α-synuclein
- Author
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Masatomo So, Toshimichi Fujiwara, Cesar Aguirre, Yasushi Kawata, Kensuke Ikenaka, Toshihiko Sugiki, Yuto Kimura, Keiichi Yamaguchi, Yuji Goto, and Hideki Mochizuki
- Subjects
Amyloid ,Magnetic Resonance Spectroscopy ,Protein Conformation ,Full‐Length Papers ,Amyloidogenic Proteins ,Protein aggregation ,Epigallocatechin gallate ,Biochemistry ,Catechin ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,law ,mental disorders ,Crystallization ,Solubility ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,030302 biochemistry & molecular biology ,food and beverages ,Polyphenols ,Amyloid fibril ,chemistry ,Polyphenol ,Biophysics ,alpha-Synuclein ,Thioflavin - 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, i.e., 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. This article is protected by copyright. All rights reserved.
- Published
- 2021