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.

中文翻译：

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洛伐他汀减轻突触核蛋白病细胞模型中的α-突触核蛋白聚集和磷酸化

帕金森病 (PD) 是最常见的神经退行性疾病之一。在病理学上，其特征在于神经元中 α-突触核蛋白 (α-syn) 的异常聚集。先前的临床证据表明，高胆固醇血症患者患 PD 的风险增加，而洛伐他汀使用者的风险降低。在本研究中，我们旨在研究洛伐他汀对 α-syn 聚集和磷酸化的影响。我们的结果表明，α-syn 预形成的原纤维在稳定转染了 α-syn-GFP 和 SH-SY5Y 细胞的 HEK293 细胞中诱导了 α-syn 的磷酸化和聚集，洛伐他汀以浓度依赖性方式减弱了 α-syn 的磷酸化和聚集. 此外，洛伐他汀抑制氧化应激、组蛋白乙酰化和酪蛋白激酶 2 的激酶活性。