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


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.

SUBMITTER: Semerdzhiev SA 

PROVIDER: S-EPMC8739828 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Semerdzhiev Slav A SA   Fakhree Mohammad A A MAA   Segers-Nolten Ine I   Blum Christian C   Claessens Mireille M A E MMAE  

ACS chemical neuroscience 20211203 1


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,  ...[more]

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