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| Item Type: | Article |
|---|---|
| Title: | EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers |
| Creators Name: | Ehrnhoefer, D.E., Bieschke, J., Boeddrich, A., Herbst, M., Masino, L., Lurz, R., Engemann, S., Pastore, A. and Wanker, E.E. |
| Abstract: | 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. |
| Keywords: | Amyloid, Amyloid Neuropathies, Amyloid beta-Protein, Catechin, Peptide Fragments, Protein Binding, Senile Plaques, alpha-Synuclein |
| Source: | Nature Structural & Molecular Biology |
| ISSN: | 1545-9985 |
| Publisher: | Nature Publishing Group |
| Volume: | 15 |
| Number: | 6 |
| Page Range: | 558-566 |
| Date: | June 2008 |
| Official Publication: | https://doi.org/10.1038/nsmb.1437 |
| PubMed: | View item in PubMed |
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