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Polyphenol‐solubility alters amyloid fibril formation of α‐synuclein
Author(s) -
So Masatomo,
Kimura Yuto,
Yamaguchi Keiichi,
Sugiki Toshihiko,
Fujiwara Toshimichi,
Aguirre Cesar,
Ikenaka Kensuke,
Mochizuki Hideki,
Kawata Yasushi,
Goto Yuji
Publication year - 2021
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.4130
Subject(s) - chemistry , solubility , thioflavin , fibril , amyloid (mycology) , biophysics , polyphenol , protein aggregation , nucleation , biochemistry , antioxidant , organic chemistry , alzheimer's disease , medicine , inorganic chemistry , disease , pathology , biology
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.