Chatterjee Debotri, Kurup Drishya, Smeyne Richard Jay
Department of Neurobiology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA, 19107, USA.
Department of Microbiology and Immunology, Thomas Jefferson University, 233 S 10th Street, Philadelphia, PA, 19107, USA.
NPJ Parkinsons Dis. 2025 Apr 23;11(1):86. doi: 10.1038/s41531-025-00925-0.
Post-infection sequela of several viruses have been linked with Parkinson's disease (PD). Here, we investigated whether mice infected with SARS-CoV-2 alone or in combination with two putative Parkinsonian toxins, MPTP and paraquat, increased the susceptibility to develop Parkinsonian pathology. We also examined if G2019S LRRK2 mice had any change in sensitivity to SARS-CoV-2 as well as if vaccination against this virus altered any neuropathology. Infection with WA-1/2020 or Omicron B1.1.529 strains sensitized both WT and G2019S LRRK2 mice to the neuropathological effects of a subtoxic exposure to MPTP, but not paraquat. These neuropathologies were rescued in WT mice vaccinated with mRNA- or protein-based SARS-CoV-2 vaccines. However, G2019S LRRK2 mutant mice were only protected with the protein-based vaccine. These results highlight the role of both environmental exposures and familial background on the development of Parkinsonian pathology secondary to viral infection and the benefit of vaccines in reducing these risks.
几种病毒的感染后后遗症已与帕金森病（PD）相关联。在此，我们研究了单独感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）或与两种假定的帕金森病毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和百草枯联合感染的小鼠是否会增加发生帕金森病病理改变的易感性。我们还研究了携带G2019S突变的富含亮氨酸重复激酶2（LRRK2）基因的小鼠对SARS-CoV-2的敏感性是否有任何变化，以及针对该病毒的疫苗接种是否会改变任何神经病理学状况。感染WA-1/2020或奥密克戎B1.1.529毒株会使野生型（WT）和携带G2019S突变的LRRK2小鼠对亚毒性剂量的MPTP的神经病理学影响敏感，但对百草枯不敏感。用基于信使核糖核酸（mRNA）或蛋白质的SARS-CoV-2疫苗接种的野生型小鼠的这些神经病理学改变得到了缓解。然而，携带G2019S突变的LRRK2基因敲入小鼠仅通过基于蛋白质的疫苗得到了保护。这些结果突出了环境暴露和家族背景在病毒感染继发的帕金森病病理发展中的作用，以及疫苗在降低这些风险方面的益处。
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