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Aggregation of alpha-synuclein (αS) into oligomers is critically involved in the pathogenesis of Parkinson's disease (PD). Using confocal single-molecule fluorescence spectroscopy, we have studied the effects of 14 naturally-occurring polyphenolic compounds and black tea extract on αS oligomer formation. We found that a selected group of polyphenols exhibited potent dose-dependent inhibitory activity on αS aggregation. Moreover, they were also capable of robustly disaggregating pre-formed αS oligomers. Based upon structure-activity analysis, we propose that the key molecular scaffold most effective in inhibiting and destabilizing self-assembly by αS requires: (i) aromatic elements for binding to the αS monomer/oligomer and (ii) vicinal hydroxyl groups present on a single phenyl ring. These findings may guide the design of novel therapeutic drugs in PD.

Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PMID: 21443877 [PubMed - indexed for MEDLINE]



  • 2011 Apr 20;585(8):1113-20. doi: 10.1016/j.febslet.2011.03.046. Epub 2011 Mar 31. Caruana M, Högen T, Levin J, Hillmer A, Giese A, Vassallo N. Dept. of Physiology & Biochemistry, University of Malta, Msida MSD 2080, Malta.

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