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Interactions between SARS-CoV-2 N-Protein and α-Synuclein Accelerate Amyloid Formation.
Semerdzhiev, Slav A; Fakhree, Mohammad A A; Segers-Nolten, Ine; Blum, Christian; Claessens, Mireille M A E.
  • Semerdzhiev SA; Nanobiophysics, MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
  • Fakhree MAA; Nanobiophysics, MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
  • Segers-Nolten I; Nanobiophysics, MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
  • Blum C; Nanobiophysics, MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
  • Claessens MMAE; Nanobiophysics, MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
ACS Chem Neurosci ; 13(1): 143-150, 2022 01 05.
Article in English | MEDLINE | ID: covidwho-1637498
Preprint
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ABSTRACT
First cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson's disease (PD) have been reported. Currently, it is unclear if there is also a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of α-synuclein protein into amyloid fibrils characteristic for PD, we investigated the effect of the presence of SARS-CoV-2 proteins on α-synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 spike protein (S-protein) has no effect on α-synuclein aggregation, while SARS-CoV-2 nucleocapsid protein (N-protein) considerably speeds up the aggregation process. We observe the formation of multiprotein complexes and eventually amyloid fibrils. Microinjection of N-protein in SH-SY5Y cells disturbed the α-synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as molecular basis for the observed correlation between SARS-CoV-2 infections and Parkinsonism.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alpha-Synuclein / Coronavirus Nucleocapsid Proteins / Amyloid Limits: Humans Language: English Journal: ACS Chem Neurosci Year: 2022 Document Type: Article Affiliation country: Acschemneuro.1c00666

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Alpha-Synuclein / Coronavirus Nucleocapsid Proteins / Amyloid Limits: Humans Language: English Journal: ACS Chem Neurosci Year: 2022 Document Type: Article Affiliation country: Acschemneuro.1c00666