Polyphenol‐solubility alters amyloid fibril formation of α‐synuclein |
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| Authors: | Masatomo So Yuto Kimura Keiichi Yamaguchi Toshihiko Sugiki Toshimichi Fujiwara Cesar Aguirre Kensuke Ikenaka Hideki Mochizuki Yasushi Kawata Yuji Goto |
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| Institution: | 1. Institute for Protein Research, Osaka University, Osaka Japan ; 2. Department of Neurology, Graduate School of Medicine, Osaka University, Osaka Japan ; 3. Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori Japan ; 4. Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds UK ; 5. Global Center for Medical Engineering and Informatics, Osaka University, Osaka Japan |
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| 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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| Keywords: | amyloid fibril formation epigallocatechin gallate kaempferol glycoside protein aggregation salt effects solubility supersaturation α ‐ synuclein |
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