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EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity

Item Type:Article
Title:EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity
Creators Name:Bieschke, J. and Russ, J. and Friedrich, R.P. and Ehrnhoefer, D.E. and Wobst, H. and Neugebauer, K. and Wanker, E.E.
Abstract:Protein misfolding and formation of beta-sheet-rich amyloid fibrils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimer's and Parkinson's disease. Recently, we demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis. It associates with natively unfolded polypeptides and promotes the self-assembly of unstructured oligomers of a new type. Whether EGCG disassembles preformed amyloid fibrils, however, remained unclear. Here, we show that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies revealed that the compound directly binds to beta-sheet-rich aggregates and mediates the conformational change without their disassembly into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils.
Keywords:Alzheimer, Parkinson, Catechine, Misfolding, Oligomer, Animals, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:7710-7715
Date:27 April 2010
Official Publication:https://doi.org/10.1073/pnas.0910723107
PubMed:View item in PubMed

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