Tea Catechins Induce the Conversion of Preformed Lysozyme Amyloid Fibrils to Amorphous Aggregates

Abstract

Natural polyphenols are major constituents of plant foods and herbs. Numerous studies have demonstrated that natural polyphenols inhibited amyloid formation and destabilized the preformed amyloid fibrils. However, the molecular mechanism for the antiamyloidogenesis of polyphenols is still unclear and remains to be further explored. In the present study, the preformed lysozyme fibrils were used as an in vitro model to study the disruptive effects of tea catechins on amyloid fibrils. Results showed that tea catechins induced the conversion of lysozyme fibrils to amorphous aggregates and inhibited fibril-induced hemolysis. Hydroquinone also showed disruptive effect on the fibrils, whereas phenol and two typical antioxidants, ascorbic acid and alpha-tocopherol, did not affect the fibrillar structure, suggesting that polyphenolic structure is essential for fibril deposition. Correlation analyses indicate that the fibril-depositing effects were related to both the antioxidative potency and hydrophobicity of tea catechins. These findings provide new evidence for comprehensive understanding of the interaction between natural polyphenols and amyloid fibrils.

Natural Compounds May Open New Routes to Treatment of Amyloid Diseases

“…The general mechanism of EGCG has now been confirmed in various misfolded protein systems [81,95,96] and the yeast prion Sup35 [86]. However, mechanistic details seem to depend on the stability of the protein aggregates that are formed with the aid of EGCG.…”

Quinopeptide formation associated with the disruptive effect of epigallocatechin-gallate on lysozyme fibrils

“…Lysozyme fibrils were prepared according to our previous reports with minor modifications [9,19]. Briefly, hen egg white lysozyme was dissolved in HCl solution (10 mM, pH 2.0) with or without EGCG to a final concentration of 10 mg/mL (0.7 mM).…”

“…The transformation of lysozyme fibrils to amorphous aggregates by EGCG was quantitatively measured according to the method previously reported [9]. Aliquots of preformed fibrils at 12 days and an EGCG stock solution were added to Tris-HCl buffer (10 mM, pH 7.5) with or without 5 mM N-ethylmaleimide (NEM).…”

“…Hydrogen bonding, hydrophobic interactions, and aromatic stacking are suggested to be the driving forces of the anti-amyloidogenic role of polyphenols [5][6][7]. In addition, antioxidant capacity is also thought to be involved in the fibril-disrupting activity of a polyphenol [8,9]. It has been reported that the oxidized form of a polyphenol has a more potent disruptive effect on amyloid fibrils than the reduced form [7,10,11].…”

“…Recent investigations have indicated that EGCG exhibits an inhibitory effect on amyloid formation by the ␤-amyloid peptide, ␣-synuclein, and other proteins [13][14][15][16]. It has also been reported that the fibril-disrupting efficiency of a tea catechin is positively correlated with its antioxidant capacity [9,17,18]. However, there is no clear understanding of the link between redox property and the corresponding anti-amyloid activity of polyphenols.…”