A cell model to study the effect of SARS-CoV-2 infections on α-Synuclein aggregation

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. It is estimated that over 1.1 million individuals suffer from PD worldwide. It is known that alpha-Synuclein is vital in the pathology of PD. Especially the aggregation of alpha-Synuclein into amyloid fibrils. The aggregation of alpha-Synuclein disrupts healthy mitochondrial activity starting a vicious cycle that causes an increase in neural death. It is suspected that viruses could cause the initial aggregation of alpha-Synuclein into amyloid fibrils. This is based on the increase in PD patients after the Spanish flu or influenza virus (H1N1) pandemic. The SARS-CoV-2 virus shares multiple similarities to the H1N1 virus, and the symptoms caused by the SARS-CoV-2 are akin to the symptoms of PD. This led to speculation about whether SARS-CoV-2 could cause post-infectious parkinsonism. This research paper looked at the nucleocapsid protein (N-protein) of SARS-CoV-2 and its ability to aggregate alpha-Synuclein in SH-SY5Y cells. A microscale thermophoresis (MST) measurement showed that the N-protein does bind to alpha-Synuclein and a ThT aggregation assay indicated that the N-protein increases the rate at which alpha-Synuclein aggregates. The N-protein was introduced to the SH-SY5Y cells with transfection. However, after multiple attempts, no conclusions could be made as either the cell count or transfection efficiency was too low.