Title:SARS-CoV-2 Infection to Premature Neuronal Aging and
Neurodegenerative Diseases: Is there any Connection with Hypoxia?
Volume: 23
Issue: 4
Author(s): Narmadhaa Sivagurunathan and Latchoumycandane Calivarathan*
Affiliation:
- Molecular Pharmacology & Toxicology Laboratory, Department of Life Sciences, School of Life Sciences, Central
University of Tamil Nadu, Thiruvarur - 610005, Tamil Nadu, India
Keywords:
Alzheimer’s disease, COVID-19, HIF-1α, hypoxia, neurodegeneration, Parkinson’s disease.
Abstract: The pandemic of coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has become
a global concern as it leads to a spectrum of mild to severe symptoms and increases death tolls
around the world. Severe COVID-19 results in acute respiratory distress syndrome, hypoxia, and multi-
organ dysfunction. However, the long-term effects of post-COVID-19 infection are still unknown.
Based on the emerging evidence, there is a high possibility that COVID-19 infection accelerates premature
neuronal aging and increases the risk of age-related neurodegenerative diseases in mild to severely
infected patients during the post-COVID period. Several studies correlate COVID-19 infection
with neuronal effects, though the mechanism through which they contribute to the aggravation of neuroinflammation
and neurodegeneration is still under investigation. SARS-CoV-2 predominantly targets
pulmonary tissues and interferes with gas exchange, leading to systemic hypoxia. The neurons in
the brain require a constant supply of oxygen for their proper functioning, suggesting that they are
more vulnerable to any alteration in oxygen saturation level that results in neuronal injury with or
without neuroinflammation. We hypothesize that hypoxia is one of the major clinical manifestations of
severe SARS-CoV-2 infection; it directly or indirectly contributes to premature neuronal aging, neuroinflammation,
and neurodegeneration by altering the expression of various genes responsible for the
survival of the cells. This review focuses on the interplay between COVID-19 infection, hypoxia,
premature neuronal aging, and neurodegenerative diseases and provides a novel insight into the molecular
mechanisms of neurodegeneration.
