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Black tea theaflavins inhibit formation of toxic amyloid-beta and alpha-synuclein fibrils

Item Type:Article
Title:Black tea theaflavins inhibit formation of toxic amyloid-beta and alpha-synuclein fibrils
Creators Name:Grelle, G. and Otto, A. and Lorenz, M. and Frank, R.F. and Wanker, E.E. and Bieschke, J.
Abstract:Causal therapeutic approaches for amyloid diseases such as Alzheimer's and Parkinson's disease targeting toxic amyloid oligomers or fibrils are still emerging. Polyphenols from green tea, especially (-)-epigallocatechin gallate (EGCG), have recently been found to redirect amyloid formation pathways leading to the assembly of small, non-toxic aggregate structures. Here, we show that theaflavins (TF1, TF2a, TF2b, TF3), the main polyphenolic components found in fermented black tea, are potent inhibitors of amyloid-beta (A{beta}) and alpha-synuclein ({alpha}S) fibrillogenesis. Their mechanism of inhibiting amyloid formation was compared to that of two established inhibitors of amyloid formation, EGCG and congo red. All three compounds reduce the fluorescence of the amyloid indicator dye thioflavin T. Mapping the binding regions of TF3 and revealed that all three bind to two regions of the peptide, aa 12-23 and aa 24-36, albeit with different specificities. However, their mechanisms of amayloid inhibition differ. Like EGCG but unlike congo red, theaflavins stimulate the assembly of A{beta} and {alpha}S into non-toxic, spherical aggregates that are incompetent to seed amyloid formation and remodel A{beta} fibrils into non-toxic, spherical aggregates. These findings suggest that theaflavins might be useful to remove toxic amyloid deposits in Alzheimer's and Parkinson's disease brains.
Keywords:alpha-Synuclein, Amyloid, Amyloid Plaque, Antioxidants, Biflavonoids, Binding Sites, Camellia sinensis, Catechin, Congo Red, Fluorescence, Hydrophobic and Hydrophilic Interactions, Protein Denaturation, Preclinical Drug Evaluation, Tumor Cell Line, Animals, Rats
Source:Biochemistry
ISSN:0006-2960
Publisher:American Chemical Society (U.S.A.)
Volume:50
Number:49
Page Range:10624-10636
Date:13 December 2011
Official Publication:https://doi.org/10.1021/bi2012383
PubMed:View item in PubMed

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