Fig. 4

SARS-CoV-2 infection causes neurodegeneration by triggering neuroinflammation. SARS-CoV-2 infection causes activation of microglia and astrocytes, triggering a neuroinflammatory cascade. Activated microglia secrete inflammatory cytokines, which promote astrocyte activation and NLRP3 inflammasome formation. Binding of SARS-CoV-2 to ACE2 downregulates ACE2 expression, which may increase Ang II expression and subsequently activate AT1R in microglia, resulting in NF-κB expression and a proinflammatory response. On the other hand, downregulation of ACE2 activity is associated with decreased Ang (1–7) levels and subsequent MasR activity in astrocytes, which may lead to the production of ROS and proinflammatory factors in the CNS parenchyma and cerebral vessels. These processes result in Aβ deposition and tau phosphorylation, which ultimately lead to neurodegeneration and AD