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Lovastatin alleviates α-synuclein aggregation and phosphorylation in cellular models of synucleinopathy
Frontiers in Molecular Neuroscience  (IF5.639),  Pub Date : 2021-06-15, DOI: 10.3389/fnmol.2021.682320
Lijun Dai, Jiannan Wang, Mingyang He, Min Xiong, Chaoyang Liu, Zhentao Zhang

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Pathologically, it is characterized by the aberrant aggregation of α-synuclein (α-syn) in neurons. Previous clinical evidence shows that patients with hypercholesterolemia are at increased risk of PD, while lovastatin users are at a reduced risk. In this study, we aimed to investigate the effect of lovastatin on the aggregation and phosphorylation of α-syn. Our results demonstrated that α-syn preformed fibrils induced the phosphorylation and aggregation of α-syn in HEK293 cells stably transfected with α-syn-GFP and SH-SY5Y cells, and lovastatin attenuated α-syn phosphorylation and aggregation in a concentration-dependent manner. Moreover, lovastatin inhibited oxidative stress, histone acetylation, and the kinase activity of casein kinase 2. Collectively, our results revealed that lovastatin alleviates α-syn aggregation and phosphorylation in cellular models of synucleinopathy, and can be a potential therapeutic drug for PD.