Ross, AlysiaXing, ViktoriaWang, Ting TBureau, Samantha CLink, Giovana AFortin, TeresaZhang, HuiHayley, ShawnSun, Hongyu2020-08-042020-08-042020-07-31Molecular Brain. 2020 Jul 31;13(1):108https://doi.org/10.1186/s13041-020-00648-8https://doi.org/10.20381/ruor-25024http://hdl.handle.net/10393/40798Abstract Parkinson’s disease (PD) is characterized by the formation of toxic, fibrillar form alpha-synuclein (α-Syn) protein aggregates in dopaminergic neurons. Accumulating evidence has shown a multifactorial interplay between the intracellular calcium elevation and α-Syn dynamics. However, whether membrane depolarization regulates toxic α-Syn aggregates remains unclear. To understand this better, we used an in vitro α-Syn preformed fibrils (PFF) model of PD in human neural cells. We demonstrated functional membrane depolarization in differentiated SH-SY5Y cells induced by two independent treatments: high extracellular K+ and the GABAA receptor blocker picrotoxin. We then observed that these treatments significantly alleviated toxic α-Syn aggregation in PFF-treated SH-SY5Y cells. Moreover, clinically relevant direct current stimulation (DCS) also remarkably decreased toxic α-Syn aggregation in PFF-treated SH-SY5Y cells. Taken together, our findings suggest that membrane depolarization plays an important role in alleviating PFF-induced toxic α-Syn aggregates, and that it may represent a novel therapeutic mechanism for PD.Journal Article2020-08-04enThe Author(s)