• Cinzia Sindona, Giovanni Schepici, Valentina Contestabile, Placido Bramanti, and Emanuela Mazzon.
• IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
• Medicina (Kaunas). 2021 Jun 11; 57 (6).

AbstractCoronavirus disease 2019 (COVID-19) is a rapidly spreading contagious infectious disease caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that primarily affects the respiratory tract as well as the central nervous system (CNS). SARS-CoV-2 infection occurs through the interaction of the viral protein Spike with the angiotensin II receptor (ACE 2), leading to an increase of angiotensin II and activation of nicotinamide adenine dinucleotide phosphate oxidase2 (NOX2), resulting in the release of both reactive oxygen species (ROS) and inflammatory molecules. The purpose of the review is to explain that SARS-CoV-2 infection can determine neuroinflammation that induces NOX2 activation in microglia. To better understand the role of NOX2 in inflammation, an overview of its involvement in neurodegenerative diseases (NDs) such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) is provided. To write this manuscript, we performed a PubMed search to evaluate the possible relationship of SARS-CoV-2 infection in NOX2 activation in microglia, as well as the role of NOX2 in NDs. Several studies highlighted that NOX2 activation in microglia amplifies neuroinflammation. To date, there is no clinical treatment capable of counteracting its activation, however, NOX2 could be a promising pharmaceutical target useful for both the treatment and prevention of NDs and COVID-19 treatment.

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