Exploring the Role of SARS-CoV-2 in Neuroinflammation: Impact on P2X7 Receptor and Neurodegenerative Diseases

Neurodegenerative diseases primarily affect the brain, leading to loss of attention, awareness, and alertness in humans. COVID-19, caused by SARS-CoV-2, has raised concerns among researchers and medical professionals due to its potential to induce neurodegenerative disorders. Despite global reports of neurological symptoms, the long-term effects of SARS-CoV-2 on the nervous system remain unclear. Complications from COVID-19 are linked to intensified immuneinflammatory reactions to the virus. SARS-CoV-2 can enter the brain via the olfactory nerve, disruption of the blood-brain barrier, or trafficking of infected immune cells across this barrier. This invasion triggers a "cytokine storm," releasing pro-inflammatory molecules into the bloodstream. Neuropsychiatric disorders and neurodegenerative diseases are often associated with neurological inflammation, blood loss, and neuron destruction caused by inflammatory mediators and viruses crossing the blood-brain barrier into the central nervous system. Consequently, SARS-CoV-2 infection may cause or worsen brain issues. Patients with conditions related to neuroimmune activation, such as Parkinson's and Alzheimer's diseases, may experience severe symptoms following SARS-CoV-2 infection. A significant factor in neuro-invasion and subsequent neuroinflammatory processes in psychiatric and neurodegenerative diseases is the stimulation of the NLRP3 inflammasome, potentially triggered by elevated extracellular ATP levels from SARS-CoV-2 infection. P2X7 receptors (P2X7Rs) in immune cells play a critical role in neuroinflammation by promoting the release of proinflammatory cytokines and ATP. These receptors contribute to the severe respiratory and neurological symptoms in COVID-19 patients, suggesting that P2X7R antagonists could be crucial in treating or preventing neurological side effects in these patients.