AUTHOR=Dai Lijun , Wang Jiannan , He Mingyang , Xiong Min , Tian Ye , Liu Chaoyang , Zhang Zhentao 

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

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 14 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.682320

DOI=10.3389/fnmol.2021.682320

ISSN=1662-5099

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. 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.