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.

Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration

“…Additionally, SARS-CoV-2-induced iron dysregulation contributes to ROS generation, fostering the pro-oxidative environment, ER stress, and the ensuing cell death [267]. The resulting imbalance in ROS homeostasis induces neuroinflammation, demyelination, and axonal damage, resembling mechanisms observed in neurodegenerative disorders like AD and PD.…”

“…SARS-CoV-2 has been associated with various short-and long-term neurological manifestations, ranging from mild symptoms to severe complications [6][7][8]262,263]. Similarly to other viruses, SARS-CoV-2 can exacerbate existing neurodegenerative conditions or contribute to their development through mechanisms such as neuroinflammation, protein aggregation, ER stress and oxidative stress [42,164,240,261,[264][265][266][267][268][269][270][271]. For instance, recent studies reveal SARS-CoV-2 targeting cortical neurons, inducing MAPT/tau pathologies and neurodegeneration [164,272].…”

“…This activation triggers the release of proinflammatory cytokines such as IL-1, IL-2, IL-6, IL-8, IL-12, and TNFα, resulting in a cytokine storm. The excessive inflammation, characteristic of severe COVID-19, stimulates the overproduction of ROS, including superoxide anion radicals, which further induces the activation of the NF-κB pathway [267,278,279].…”

Acute and chronic central nervous system oxidative stress/toxicity during hyperbaric oxygen treatment of subacute and chronic neurological conditions

“…Given the non-prospective nature of this study documentation with biomarkers would have required pre/post sampling which was impossible in a retrospective study. While many biomarkers of OT are available today (85)(86)(87)(88)(89)(90), none are routinely used in clinical hyperbaric medicine practice, and the results are mixed in their use in clinical hyperbaric oxygen studies (91). Future clinical studies on hyperbaric CNS OT should employ biomarkers.…”