Scientists have identified an emerging pattern of associations between SARS-CoV-2 (the virus that causes COVID-19) and Parkinson’s disease. For example, the loss of smell is one of the most common symptoms reported in SARS-CoV-2 infection, but it is also an early symptom of Parkinson’s disease, often preceding diagnosis by many years. In addition, some recent case reports describe patients who presented with probable Parkinson’s disease after recovering from severe SARS-CoV-2 infection. Now, evidence from a recent study suggests that the SARS-CoV-2 nucleocapsid protein drives aggregation of alpha synuclein, a hallmark of Parkinson’s disease.

SARS-CoV-2 nucleocapsid proteins are helical structures that are housed within the viral membrane. They encapsulate SARS-CoV-2’s genome, protecting it from the host cellular environment. The virus produces large quantities of nucleocapsid proteins once inside an infected cell because they play critical roles in virion assembly and viral replication.

Alpha synuclein is a type of neuronal protein that regulates synaptic vesicle movements and neurotransmitter release. Its aggregation, a progressive process that spreads from cell to cell, impairing brain function, is a dominant feature in the pathophysiology of Parkinson’s disease.

The authors of the report assessed alpha synuclein aggregation in both the absence and presence of the SARS-CoV-2 spike protein (the virus’s primary infectious particle) and the nucleocapsid protein. They found that in the absence of any SARS-CoV-2 proteins, aggregation naturally occurred after about 10 days. The spike protein had no effect on aggregation time, but following exposure to the nucleocapsid protein, aggregation occurred in less than one day – more than 10 times faster than normal.

Then they studied the effects of the nucleocapsid protein in a cell model of Parkinson’s disease. They injected some of the cells with nucleocapsid protein (about the amount one would expect during SARS-CoV-2 infection) and alpha synuclein and injected some with alpha synuclein alone. They found that twice as many cells injected with both proteins died compared to those injected with alpha synuclein alone.

These findings suggest that the SARS-CoV-2 nucleocapsid protein drives aggregation of alpha synuclein and promotes cells death in a model of Parkinson’s disease. Learn more about Parkinson’s disease in this episode featuring Dr. Gizelle Petzinger.

• Link to full publication.