Figure 3.

The hypothesized mechanism of coronavirus-induced neuronal damage via oxidative stress and mitochondria dysfunction. SARS-CoV-2 infection occurs when TMPRSS2 primes the spike proteins for proteolysis, allowing the binding to ACE2. The affinity interaction triggers the binding of Ang II to the angiotensin type 1 receptor (AT1R), activating NADPH oxidase. This leads to mitochondrial electron transport chain (ETC) damage via the release of oxidative and nitrosative species, subsequently increasing the formation of mitochondrial reactive oxygen species (mtROS). The signaling pathways mediated by mtROS trigger the production of inflammatory cytokines, which can compromise the blood–brain barrier, thus resulting in neuronal damage. Additionally, mtROS cause nuclear and mitochondrial damage, which prolongs mitochondrial dysfunction and encourages inflammatory senescence (created with BioRender).