Alleviating toxic α-Synuclein accumulation by membrane depolarization: evidence from an in vitro model of Parkinson’s disease

Autor: Hui Zhang, Shawn Hayley, Viktoria Xing, Samantha C. Bureau, Ting Ting Wang, Hongyu Sun, Teresa Fortin, Giovana A. Link, Alysia Ross
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecular Brain, Vol 13, Iss 1, Pp 1-11 (2020)
Molecular Brain
ISSN: 1756-6606
DOI: 10.1186/s13041-020-00648-8
Popis: 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.
Databáze: OpenAIRE
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