Interactions between SARS-CoV-2 N-Protein and α-Synuclein Accelerate Amyloid Formation.
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.
['Semerdzhiev|Slav A|SA|https://orcid.org/0000-0002-7594-0641', 'Fakhree|Mohammad A A|MAA|https://orcid.org/0000-0002-8559-1377', 'Segers-Nolten|Ine|I|', 'Blum|Christian|C|https://orcid.org/0000-0002-6524-2495', 'Claessens|Mireille M A E|MMAE|https://orcid.org/0000-0002-2206-4422']
SARS-CoV-2 amyloids Covid-19 Parkinson’s disease neurodegeneration protein aggregation