title: Black tea theaflavins inhibit formation of toxic amyloid-β and α-synuclein fibrils.
abstract: Causal therapeutic approaches for amyloid diseases such as Alzheimer's and Parkinson's disease targeting toxic amyloid oligomers or fibrils are still emerging. Here, we show that theaflavins (TF1, TF2a, TF2b, and TF3), the main polyphenolic components found in fermented black tea, are potent inhibitors of amyloid-β (Aβ) and α-synuclein (αS) fibrillogenesis. Their mechanism of action was compared to that of two established inhibitors of amyloid formation, (-)-epigallocatechin gallate (EGCG) and congo red (CR). All three compounds reduce the fluorescence of the amyloid indicator dye thioflavin T. Mapping the binding regions of TF3, EGCG, and CR revealed that all three bind to two regions of the Aβ peptide, amino acids 12-23 and 24-36, albeit with different specificities. However, their mechanisms of amyloid inhibition differ. Like EGCG but unlike congo red, theaflavins stimulate the assembly of Aβ and αS into nontoxic, spherical aggregates that are incompetent in seeding amyloid formation and remodel Aβ fibrils into nontoxic aggregates. When compared to EGCG, TF3 was less susceptible to air oxidation and had an increased efficacy under oxidizing conditions. These findings suggest that theaflavins might be used to remove toxic amyloid deposits.
authors: Max Delbrück Centrum für Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany.
authors: Gerlinde
authors: G
authors: Grelle
authors: Albrecht
authors: A
authors: Otto
authors: Mario
authors: M
authors: Lorenz
authors: Ronald F
authors: RF
authors: Frank
authors: Erich E
authors: EE
authors: Wanker
authors: Jan
authors: J
authors: Bieschke
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D044946:Biflavonoids / Q000494:pharmacology*; D001665:Binding Sites; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003224:Congo Red / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005453:Fluorescence; D057927:Hydrophobic and Hydrophilic Interactions; D058225:Plaque, Amyloid / Q000188:drug therapy; D011489:Protein Denaturation / Q000187:drug effects; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D044946:Biflavonoids; D051844:alpha-Synuclein; C056068:theaflavin; D003224:Congo Red; D002392:Catechin; C045651:epigallocatechin gallate