Interactions between SARS-CoV-2 N-Protein and α-Synuclein Accelerate Amyloid Formation

Slav A. Semerdzhiev, Mohammad A.A. Fakhree, Ine Segers-Nolten, Christian Blum*, Mireille M.A.E. Claessens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalACS chemical neuroscience
Volume13
Issue number1
DOIs
Publication statusPublished - 5 Jan 2022

Keywords

  • amyloids
  • Covid-19
  • neurodegeneration
  • Parkinson’s disease
  • protein aggregation
  • SARS-CoV-2
  • UT-Hybrid-D
  • Parkinson's disease

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