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The effect of SARS-CoV-2 on the development of Parkinson's disease: the role of α-synuclein

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Abstract

The current coronavirus disease 2019 (COVID-19) can lead to various neurological complications in infected people. These neurological effects include problems in both central nervous system (CNS) and peripheral nervous system (PNS). Hyposmia, a PNS symptom of COVID-19, frequently manifests in the early stages of Parkinson's disease (PD) and serves as an early warning sign of the condition. In addition, the olfactory system is recognized as an early site for the onset of α-synuclein pathology, the pathological hallmark of PD. PD is characterized by accumulation and aggregation of misfolded α-synuclein (α-Syn) into Lewy bodies and Lewy neurites, resulting in the degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Previous research has also shown the involvement of α-Syn in the innate immune response following viral infections. Consequently, the potential link between viral infections and development of PD has gained attention in recent years. However, it's still too early to definitively conclude whether COVID-19 can cause Parkinsonism. Nevertheless, we can explore the likelihood of this connection by examining past studies and possible mechanisms to better understand how COVID-19 might potentially lead to PD following the infection. Based on the various pieces of evidence discussed in this review, we can infer that SARS-CoV-2 promotes the aggregation of α-Syn and, ultimately, leads to PD through at least two mechanisms: the stable binding of the S1 protein to proteins prone to aggregation like α-Syn, and the upregulation of α-Syn as part of the immune response to the infection.

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  1. Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Farideh Iravanpour, Majid Reza Farrokhi, Morteza Jafarinia & Razieh Tavakoli Oliaee

  2. Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran

    Majid Reza Farrokhi

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FI conceived the idea and wrote the first draft of the paper. MRF revised subsequent drafts. RTO and MJ supervised, contributed to the conception, critical review, and revision of the paper. All authors approved the final draft for submission.

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Iravanpour, F., Farrokhi, M.R., Jafarinia, M. et al. The effect of SARS-CoV-2 on the development of Parkinson's disease: the role of α-synuclein. Human Cell 37, 1–8 (2024). https://doi.org/10.1007/s13577-023-00988-2

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