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

• DOI: 10.1021/acschemneuro.1c00666
• Publication Date: 2021-12-03T13:31:54Z
• Authors: Slav A. Semerdzhiev; Mohammad A. A. Fa...; Ine Segers-Nolten; Christian Blum; Mireille M. A. E....
• Keywords: 0301 basic medicine; Amyloid; SARS-CoV-2; Parkinson's disease; neurodegeneration; UT-Hybrid-D; COVID-19; Phosphoproteins; protein aggregation; 3. Good health; 03 medical and health sciences; Spike Glycoprotein, Coronavirus; Parkinson’s disease; alpha-Synuclein; Coronavirus Nucleocapsid Proteins; Humans; amyloids; Covid-19

AbstractFirst cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson’s disease have been reported. Currently it is unclear if there also is 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 Parkinson’s disease, 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 S-protein has no effect on α-synuclein aggregation while SARS-CoV-2 N-protein considerably speeds up the aggregation process. We observe the formation of multi-protein complexes, and eventually amyloid fibrils. Microinjection of N-protein in SHSY-5Y 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 coincidence between SARS-CoV-2 infections and Parkinsonism.