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The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections
Arnaud John Kombe Kombe1, Leila Fotoohabadi1, Ravikanth Nanduri1
1Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Abstract:
Respiratory viruses constitute a significant cause of illness and death worldwide. Respiratory virus-associated injuries include oxidative stress, ferroptosis, inflammation, pyroptosis, apoptosis, fibrosis, autoimmunity, and vascular injury. Several studies have demonstrated the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) in the pathophysiology of viral infection and associated complications. It has thus emerged as a pivotal player in cellular defense mechanisms against such damage. Here, we discuss the impact of Nrf2 activation on airway injuries induced by respiratory viruses, including viruses, coronaviruses, rhinoviruses, and respiratory syncytial viruses. The inhibition or deregulation of Nrf2 pathway activation induces airway tissue damage in the presence of viral respiratory infections. In contrast, Nrf2 pathway activation demonstrates protection against tissue and organ injuries. Clinical trials involving Nrf2 agonists are needed to define the effect of Nrf2 therapeutics on airway tissues and organs damaged by viral respiratory infections.
Insights
Nuclear factor erythroid 2-related factor 2 (Nrf2) activation protects against respiratory virus-induced airway injuries. Nrf2 pathway deregulation exacerbates damage, highlighting its therapeutic potential.
Area of Science:
- * Molecular biology and immunology
- * Pathophysiology of respiratory viral infections
Background:
- * Respiratory viruses cause significant global morbidity and mortality.
- * Associated injuries include oxidative stress, inflammation, and tissue damage.
- * The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is implicated in cellular defense against viral damage.
Purpose of the Study:
- * To review the role of Nrf2 activation in mitigating airway injuries caused by respiratory viruses.
- * To discuss the impact of Nrf2 pathway status on viral-induced tissue damage.
- * To highlight the potential of Nrf2 agonists as therapeutics for viral respiratory infections.
Main Methods:
- * Literature review of studies investigating Nrf2 in viral respiratory infections.
- * Analysis of Nrf2's involvement in cellular defense mechanisms.
- * Examination of Nrf2's impact on various respiratory viruses (e.g., influenza, coronaviruses, rhinoviruses, RSV).
Main Results:
- * Nrf2 pathway activation demonstrates protective effects against respiratory virus-induced airway and organ injuries.
- * Inhibition or deregulation of Nrf2 exacerbates tissue damage during viral respiratory infections.
- * Nrf2 plays a pivotal role in cellular defense against viral pathogens and associated complications.
Conclusions:
- * Nrf2 activation is a key protective mechanism against respiratory virus-induced airway injuries.
- * Targeting the Nrf2 pathway may offer therapeutic benefits for managing viral respiratory infections.
- * Clinical trials are necessary to evaluate Nrf2 agonists for treating viral respiratory damage.
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