{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["107(17)"],"submitter":["Bieschke J"],"pubmed_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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["7710-5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2867908"],"repository":["biostudies-literature"],"pubmed_title":["EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity."],"pmcid":["PMC2867908"],"pubmed_authors":["Wobst H","Bieschke J","Friedrich RP","Ehrnhoefer DE","Neugebauer K","Wanker EE","Russ J"],"additional_accession":[]},"is_claimable":false,"name":"EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity.","description":"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.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Apr","modification":"2025-04-21T16:11:21.753Z","creation":"2019-03-27T00:30:44Z"},"accession":"S-EPMC2867908","cross_references":{"pubmed":["20385841"],"doi":["10.1073/pnas.0910723107"]}}