An interaction between SARS-CoV-2 nucleoprotein with α-synuclein may accelerate the formation of amyloid fibrils and provide the molecular basis for the observed correlation between SARS-CoV-2 infection and Parkinsonism, according to study results published in the journal ACS Chemical Neuroscience.
Previous studies have shown that SARS-CoV-2 infection may be associated with neurological complications and there are reports of cases of Parkinsonism in relatively young patients with a history of SARS-CoV-2 infection.
As data on the direct causal link between the diseases are limited, the objective of the current study was to explore the potential molecular basis for the association between the viral infection and the development of Parkinsonism. The nucleocapsid protein and spike protein are the most abundant soluble structural SARS-CoV-2 proteins and the interaction between α-synuclein and these proteins and the impact on aggregation of α-synuclein into amyloid fibrils were determined.
Test tube experiments showed that SARS-CoV-2 spike protein has no effect on α-synuclein aggregation. However, nucleocapsid protein significantly accelerated the aggregation process following a direct interaction between α-synuclein and nucleocapsid protein resulting in the formation of complexes that contain multiple protein and eventually amyloid fibrils.
Using SH-SY5Y cells, neuronal cells that express α-synuclein and are widely used as neuronal cell model in Parkinson disease, the researchers showed that microinjection of nucleocapsid protein distributed the α-synuclein proteostasis and increased cell death.
“Our results point toward a direct interaction between the N-protein [nucleocapsid protein] of SARS-CoV-2 and αS [α-synuclein] as a molecular basis for the observed relations between virus infections and Parkinsonism. The observed molecular interactions thus suggest that SARS-CoV-2 infections may have long-term implications and that caution is required in considering N-protein as an alternative target in vaccination strategies,” concluded the researchers.
Semerdzhiev SA, Fakhree MAA, Segers-Nolten I, Blum C, Claessens MMAE. Interactions between SARS-CoV-2 N-protein and α-synuclein accelerate amyloid formation. ACS Chem Neurosci. Published online, December 3, 2021. doi: 10.1021/acschemneuro.1c00666