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.

中文翻译：

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多酚溶解度改变 α-突触核蛋白的淀粉样蛋白原纤维形成

淀粉样蛋白原纤维的形成与各种淀粉样变性有关，包括阿尔茨海默病和帕金森病等神经退行性疾病。淀粉样原纤维在打破过饱和时形成高于淀粉样蛋白或肽的溶解度，随后是成核和伸长机制，类似于溶质的结晶。许多添加剂，包括盐、去污剂和天然化合物，可促进或抑制淀粉样蛋白的形成。然而，相反作用的潜在机制尚不清楚。我们研究了两种多酚，即表没食子儿茶素没食子酸酯 (EGCG) 和山柰酚-7─O─糖苷 (KG)，分别具有高和低溶解度，对 α-突触核蛋白 (αSN) 的淀粉样蛋白形成的影响。EGCG 和 KG 分别抑制和促进 αSN 的淀粉样蛋白形成，当通过硫代黄素 T (ThT) 荧光或透射电子显微镜 (TEM) 监测时。核磁共振（NMR）分析表明，虽然αSN与可溶性EGCG的相互作用增加了αSN的溶解度，从而抑制了淀粉样蛋白的形成，但αSN与不溶性KG的相互作用降低了αSN的溶解度，从而促进了淀粉样蛋白的形成。我们的研究表明，多酚对蛋白质和肽的淀粉样蛋白形成的相反影响可以根据多酚的溶解度来解释。从而促进淀粉样蛋白的形成。我们的研究表明，多酚对蛋白质和肽的淀粉样蛋白形成的相反影响可以根据多酚的溶解度来解释。从而促进淀粉样蛋白的形成。我们的研究表明，多酚对蛋白质和肽的淀粉样蛋白形成的相反影响可以根据多酚的溶解度来解释。