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Updated: Jun 3, 2026

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
Published on: November 25, 2022
Inhibition and disaggregation of α-synuclein oligomers by natural polyphenolic compounds
Mario Caruana1, Tobias Högen, Johannes Levin
1Dept. of Physiology & Biochemistry, University of Malta, Msida MSD 2080, Malta.
Abstract:
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.
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