Piceatannol and Other Wine Stilbenes: A Pool of Inhibitors against α-Synuclein Aggregation and Cytotoxicity

The aggregation of alpha-synuclein is one on the key pathogenic events in Parkinson's disease. In the present study, we investigated the inhibitory capacities of stilbenes against alpha-synuclein aggregation and toxicity. Thioflavin T fluorescence, transmission electronic microscopy, and SDS-PAGE analysis were performed to investigate the inhibitory effects of three stilbenes against alpha-synuclein aggregation: piceatannol, ampelopsin A, and isohopeaphenol. Lipid vesicle permeabilization assays were performed to screen stilbenes for protection against membrane damage induced by aggregated alpha-synuclein. The viability of PC12 cells was examined using an MTT assay to assess the preventive effects of stilbenes against alpha-synuclein-induced toxicity. Piceatannol inhibited the formation of alpha synuclein fibrils and was able to destabilize preformed filaments. It seems to induce the formation of small soluble complexes protecting membranes against alpha-synuclein-induced damage. Finally, piceatannol protected cells against alpha-synuclein-induced toxicity. The oligomers tested (ampelopsin A and hopeaphenol) were less active.