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Lovastatin Alleviates α-Synuclein Aggregation and Phosphorylation in Cellular Models of Synucleinopathy

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. Clinical evidence shows that patients with… Click to show full abstract

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. Clinical evidence shows that patients with hypercholesterolemia are more likely to get PD, while lovastatin users have a lower risk of suffering from it. In this study, we investigated the effects of lovastatin on the aggregation and phosphorylation of α-syn in vitro. Our results demonstrate that α-syn preformed fibrils induce the phosphorylation and aggregation of α-syn in HEK293 cells stably transfected with α-syn-GFP and SH-SY5Y cells as well, which could be attenuated by in a concentration-dependent manner. Besides, lovastatin inhibited oxidative stress, histone acetylation, and the activation of casein kinase 2 (CK2). Collectively, lovastatin alleviates α-syn aggregation and phosphorylation in cellular models of synucleinopathy, indicating its potential value of being adopted in the management of PD.

Keywords: lovastatin alleviates; aggregation; aggregation phosphorylation; cellular models; phosphorylation cellular; phosphorylation

Journal Title: Frontiers in Molecular Neuroscience
Year Published: 2021

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