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

被引：11

作者：

Dai, Lijun ^{[1
]}

Wang, Jiannan ^{[1
]}

He, Mingyang ^{[2
]}

Xiong, Min ^{[1
]}

Tian, Ye ^{[1
]}

Liu, Chaoyang ^{[1
,3
]}

Zhang, Zhentao ^{[1
]}

机构：

[1] Wuhan Univ, Dept Neurol, Renmin Hosp, Wuhan, Peoples R China

[2] Hubei Prov Inst Food Supervis & Test, Wuhan, Peoples R China

[3] Zhongnan Univ Econ & Law, Res Ctr Environm & Hlth, Wuhan, Peoples R China

来源：

FRONTIERS IN MOLECULAR NEUROSCIENCE | 2021年 / 14卷

基金：

中国国家自然科学基金;

关键词：

Parkinson's disease; protein aggregation; alpha-synuclein; statins; casein kinase 2; haistone acetylation; PARKINSON DISEASE; STATIN THERAPY; IN-VITRO; RISK; ONSET;

D O I：

10.3389/fnmol.2021.682320

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Pathologically, it is characterized by the aberrant aggregation of alpha-synuclein (alpha-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 alpha-syn in vitro. Our results demonstrate that alpha-syn preformed fibrils induce the phosphorylation and aggregation of alpha-syn in HEK293 cells stably transfected with alpha-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 alpha-syn aggregation and phosphorylation in cellular models of synucleinopathy, indicating its potential value of being adopted in the management of PD.

引用

页数：12

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