Cascading from SARS-CoV-2 to Parkinson's Disease through Protein-Protein Interactions

Area of Science:

• Neuroscience
• Virology
• Molecular Biology

Background:

• Coronavirus disease (COVID-19) can cause extrapulmonary damage, including to the central nervous system (CNS).
• A few cases suggest a link between COVID-19 and Parkinson's disease (PD), but existing hypotheses are insufficient.
• Understanding the molecular mechanisms is crucial for exploring potential CNS damage in COVID-19 patients.

Purpose of the Study:

• To propose a molecular-level mechanistic hypothesis explaining the link between COVID-19 and Parkinson's disease (PD).
• To explore potential CNS damage in COVID-19 patients through a novel model.
• To identify specific molecular pathways involved in the cascade from lung infection to neurodegeneration.

Main Methods:

• Development of a model using bioinformatic tools to illustrate the cascade effects from COVID-19 to the CNS.
• Identification of host proteins in the lungs modified by viral proteins and transported via exosomes.
• Analysis of protein-protein interactions in the CNS disrupted by these modified host proteins, focusing on PD-associated proteins.

Main Results:

• Identified 44 CNS proteins associated with PD, whose interactions can be perturbed by 24 lung-expressed host proteins.
• These 24 host proteins interact with viral proteins and are found in exosome cargoes, linking lung infection to systemic effects.
• A tightly connected network was observed between perturbator proteins and PD-vulnerable proteins, suggesting a specific molecular pathway.

Conclusions:

• The proposed hypothesis provides a molecular basis for the cascading effects of COVID-19 from the lungs to the CNS, potentially causing Parkinsonism.
• Disruption of autophagy/ubiquitination processes appears critical, leading to increased exosome generation carrying perturbators that affect PD-vulnerable proteins.
• This mechanistic model offers a framework for further research into COVID-19-induced neurodegenerative conditions.