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Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells.
Limanaqi, Fiona; Zecchini, Silvia; Saulle, Irma; Strizzi, Sergio; Vanetti, Claudia; Garziano, Micaela; Cappelletti, Gioia; Parolin, Debora; Caccia, Sonia; Trabattoni, Daria; Fenizia, Claudio; Clerici, Mario; Biasin, Mara.
Afiliação
  • Limanaqi F; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy. fiona.limanaqi@unimi.it.
  • Zecchini S; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Saulle I; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Strizzi S; Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, Milan, Italy.
  • Vanetti C; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Garziano M; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Cappelletti G; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Parolin D; Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza, Milan, Italy.
  • Caccia S; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Trabattoni D; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Fenizia C; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Clerici M; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
  • Biasin M; Department of Biomedical and Clinical Sciences, University of Milan, Via G.B. Grassi, Milan, Italy.
Biol Res ; 57(1): 2, 2024 Jan 09.
Article em En | MEDLINE | ID: mdl-38191441
ABSTRACT

BACKGROUND:

Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection.

RESULTS:

Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimermonomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimermonomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimermonomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimermonomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimermonomer equilibrium.

CONCLUSIONS:

Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interferon Tipo I / Alfa-Sinucleína / SARS-CoV-2 / COVID-19 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Itália País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interferon Tipo I / Alfa-Sinucleína / SARS-CoV-2 / COVID-19 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Itália País de publicação: Reino Unido