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. 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.