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

Area of Science:

• Neuroscience
• Virology
• Molecular Biology

Background:

• Emerging cases suggest a correlation between SARS-CoV-2 infection and Parkinson's disease (PD) development.
• The direct causal link and molecular mechanisms underlying this association remain unclear.
• Alpha-synuclein protein aggregation into amyloid fibrils is a hallmark of Parkinson's disease.

Purpose of the Study:

• To investigate the molecular interaction between SARS-CoV-2 proteins and alpha-synuclein aggregation.
• To determine if viral proteins can influence the formation of alpha-synuclein amyloid fibrils.

Main Methods:

• In vitro experiments assessing the effect of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins on alpha-synuclein aggregation.
• Observation of multiprotein complex and amyloid fibril formation.
• Microinjection of N-protein into SH-SY5Y cells to evaluate effects on alpha-synuclein proteostasis and cell viability.

Main Results:

• SARS-CoV-2 S-protein did not affect alpha-synuclein aggregation.
• SARS-CoV-2 N-protein significantly accelerated alpha-synuclein aggregation, leading to multiprotein complexes and amyloid fibrils.
• N-protein microinjection disrupted alpha-synuclein proteostasis and increased cell death in SH-SY5Y cells.

Conclusions:

• Direct interaction between SARS-CoV-2 N-protein and alpha-synuclein is demonstrated.
• This interaction provides a potential molecular basis for the observed correlation between SARS-CoV-2 infection and Parkinsonism.
• The findings suggest a mechanistic link between viral infection and neurodegenerative processes characteristic of PD.