Wu Zhengcun, Zhang Xiuao, Huang Zhangqiong, Ma Kaili
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Medical Primate Research Center & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Int J Mol Sci. 2022 Mar 21;23(6):3394. doi: 10.3390/ijms23063394.
Growing cases of patients reported have shown a potential relationship between (severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection and Parkinson's disease (PD). However, it is unclear whether there is a molecular link between these two diseases. Alpha-synuclein (α-Syn), an aggregation-prone protein, is considered a crucial factor in PD pathology. In this study, bioinformatics analysis confirmed favorable binding affinity between α-Syn and SARS-CoV-2 spike (S) protein and nucleocapsid (N) protein, and direct interactions were further verified in HEK293 cells. The expression of α-Syn was upregulated and its aggregation was accelerated by S protein and N protein. It was noticed that SARS-CoV-2 proteins caused Lewy-like pathology in the presence of α-Syn overexpression. By confirming that SARS-CoV-2 proteins directly interact with α-Syn, our study offered new insights into the mechanism underlying the development of PD on the background of COVID-19.
报告的患者病例不断增加，显示出严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染与帕金森病（PD）之间存在潜在联系。然而，这两种疾病之间是否存在分子联系尚不清楚。α-突触核蛋白（α-Syn）是一种易于聚集的蛋白质，被认为是帕金森病病理学中的关键因素。在本研究中，生物信息学分析证实了α-Syn与SARS-CoV-2刺突（S）蛋白和核衣壳（N）蛋白之间具有良好的结合亲和力，并在HEK293细胞中进一步验证了直接相互作用。S蛋白和N蛋白上调了α-Syn的表达并加速了其聚集。值得注意的是，在α-Syn过表达的情况下，SARS-CoV-2蛋白导致了路易体样病理变化。通过证实SARS-CoV-2蛋白与α-Syn直接相互作用，我们的研究为在COVID-19背景下帕金森病发展的潜在机制提供了新的见解。
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