Oxidative stress and COVID-19-associated neuronal dysfunction: mechanisms and therapeutic implications

Abstract

Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19), and there is a possible role for oxidative stress in the pathophysiology of neurological diseases associated with COVID-19. Excessive oxidative stress could be responsible for the thrombosis and other neuronal dysfunctions observed in COVID-19. This review discusses the role of oxidative stress associated with SARS-CoV-2 and the mechanisms involved. Furthermore, the various therapeutics implicated in treating COVID-19 and the oxidative stress that contributes to the etiology and pathogenesis of COVID-19-induced neuronal dysfunction are discussed. Further mechanistic and clinical research to combat COVID-19 is warranted to understand the exact mechanisms, and its true clinical effects need to be investigated to minimize neurological complications from COVID-19.

Keywords: COVID-19; antioxidants; cytokine storm; neuronal dysfunction; oxidative stress.

Figure 1

Toll-like receptor signaling pathways TLR1/2, TLR2/6 and TLR4 are in the cell membrane. TLR1/2 and TLR2/6 activate the MyD88 pathway, while TLR4 activates both the TRIF pathway and the MyD88 pathway. TLR3, TLR7, TLR8, and TLR9 are located inside endosomes. TLR3 activates the TRIF pathway, and TLR7, TLR8, and TLR9 activate the MyD88 pathway. The SARS-CoV-2 virus activates TLR4 prior to entering the cell, activating both the MyD88 and TRIF pathways. SARS-CoV-2 virus does this via its spike protein.

Figure 2

In response to the activation of PAMPs signaling, NF-κB triggers the transcription of a group of inducible proinflammatory target genes involved in various cellular processes