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          Institute: MPI für molekulare Genetik     Collection: Microscopy     Display Documents



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ID: 412076.0, MPI für molekulare Genetik / Microscopy
EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers
Authors:Ehrnhoefer, Dagmar E; Bieschke, Jan; Boeddrich, Annett; Herbst, Martin; Masino, Laura; Lurz, Rudi; Engemann, Sabine; Pastore, Annalisa; Wanker, Erich E
Language:English
Date of Publication (YYYY-MM-DD):2008-05-30
Title of Journal:Nature Structural & Molecular Biology
Journal Abbrev.:Nat Struct Mol Biol
Volume:15
Issue / Number:6
Start Page:558
End Page:56
Copyright:© 2009 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Review Status:not specified
Audience:Experts Only
Abstract / Description:The accumulation of beta-sheet–rich amyloid fibrils or aggregates is a complex, multistep process that is associated with cellular toxicity in a number of human protein misfolding disorders, including Parkinson's and Alzheimer's diseases. It involves the formation of various transient and intransient, on- and off-pathway aggregate species, whose structure, size and cellular toxicity are largely unclear. Here we demonstrate redirection of amyloid fibril formation through the action of a small molecule, resulting in off-pathway, highly stable oligomers. The polyphenol (- )-epigallocatechin gallate efficiently inhibits the fibrillogenesis of both alpha-synuclein and amyloid-beta by directly binding to the natively unfolded polypeptides and preventing their conversion into toxic, on-pathway aggregation intermediates. Instead of beta-sheet–rich amyloid, the formation of unstructured, nontoxic alpha-synuclein and amyloid-beta oligomers of a new type is promoted, suggesting a generic effect on aggregation pathways in neurodegenerative diseases.
Comment of the Author/Creator:Correspondence to: Erich E Wanker1 e-mail: ewanker@mdc-berlin.de
External Publication Status:published
Document Type:Article
Communicated by:Rudi Lurz
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Max Delbrueck Center for Molecular Medicine (MDC), AG Neuroproteomics, Robert-Roessle-Stras zlige 10, 13092 Berlin, Germany;
2.National Institute for Medical Research (NIMR), The Ridgeway, Mill Hill, London NW7 1AA, UK.
Identifiers:URL:http://www.nature.com/nsmb/journal/v15/n6/pdf/nsmb...
DOI:10.1038/nsmb.1437
ISSN:1545-9993
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