title: The green tea polyphenol (-)-epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios.
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.
authors.affiliation: AstraZeneca-Tufts Lab for Basic and Translational Medicine, Boston, MA, USA(1); Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Heike J
authors.initials: HJ
authors.lastname: Wobst
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas, Southwestern Medical Center, USA.
authors.forename: Apurwa
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas, Southwestern Medical Center, USA.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Diamond
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany. Electronic address: ewanker@mdc-berlin.de.
authors.forename: Erich E
authors.initials: EE
authors.lastname: Wanker
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany; Washington University in St. Louis, Saint Louis, MO, USA. Electronic address: bieschke@wustl.edu.
authors.forename: Jan
authors.initials: J
authors.lastname: Bieschke
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016716:PC12 Cells; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013662:Tea / Q000737:chemistry*; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; C489131:Mapt protein, rat; D013662:Tea; D016875:tau Proteins; D002392:Catechin; C045651:epigallocatechin gallate
keywords: (−)-Epigallocatechin gallate; Aggregation inhibitors; Alzheimer‘s disease; Polyphenol; Tau oligomers; Tau protein