The green tea polyphenol (−)‐epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios. Issue 1 (29th November 2014)

• Record Type: Journal Article
• Authors: Wobst, Heike J.; Sharma, Apurwa; Diamond, Marc I.; Wanker, Erich E.; Bieschke, Jan
• Is Part Of: FEBS letters. Volume 589:Issue 1(2015)
• Page Start: 77
• Page End: 83
• Publication Date: 2014-11-29
• Subjects: AD -- Alzheimer's disease -- EGCG -- (−)-epigallocatechin gallate -- ThT -- Thioflavin T -- PCR -- polymerase chain reaction -- NBT -- nitroblue tetrazolium -- MTT -- 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- AFM -- atomic force microscopy -- Tau protein -- Tau oligomers -- Aggregation inhibitors -- (−)-Epigallocatechin gallate -- Alzheimer's disease -- Polyphenol; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.11.026
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The accumulation of amyloid‐beta (Aβ) and tau aggregates is a pathological hallmark of Alzheimer's disease . Both polypeptides form fibrillar deposits, but several lines of evidence indicate that Aβ and tau form toxic oligomeric aggregation intermediates. Depleting such structures could thus be a powerful therapeutic strategy. We generated a fragment of tau (His‐K18ΔK280) that forms stable, toxic, oligomeric tau aggregates in vitro. We show that (−)‐epigallocatechin gallate (EGCG), a green tea polyphenol that was previously found to reduce Aβ aggregation, inhibits the aggregation of tau K18ΔK280 into toxic oligomers at ten‐ to hundred‐fold substoichiometric concentrations, thereby rescuing toxicity in neuronal model cells. Abstract : Tau forms neurofibrillary tangles in Alzheimer's disease. Four repeat domain tau fragment K18ΔK280 aggregates into toxic oligomers without heparin. EGCG inhibits K18ΔK280 aggregation at ten‐ to hundred‐fold substoichiometric concentrations. EGCG likely sequesters and inactivates a rare nucleating tau oligomer species.