Role of Nrf2 and Its Activators in Respiratory Diseases

Area of Science:

• Molecular Biology
• Cellular Signaling
• Respiratory Medicine

Background:

• Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating antioxidant and cytoprotective gene expression via the antioxidant response element (ARE).
• Under normal conditions, Kelch-like ECH-associated protein 1 (Keap1) inhibits Nrf2 by promoting its cytoplasmic degradation.
• Oxidative stress disrupts the Keap1-Nrf2 interaction, allowing Nrf2 to translocate to the nucleus and activate protective gene expression.

Purpose of the Study:

• To review the role of Nrf2 in the pathogenesis of various respiratory diseases.
• To summarize the protective effects of Nrf2 activation in experimental models and human studies of lung disorders.
• To highlight the therapeutic potential of Nrf2 inducers for respiratory conditions.

Main Methods:

• Literature review of experimental models and human studies.
• Analysis of Nrf2's involvement in the molecular mechanisms of respiratory diseases.
• Examination of the efficacy of Nrf2 activators in preclinical and clinical settings.

Main Results:

• Nrf2 deletion exacerbates injury and severity in models of bronchopulmonary dysplasia, respiratory infections, ARDS, COPD, asthma, IPF, and lung cancer.
• Nrf2 activation demonstrates protective effects across a spectrum of respiratory diseases.
• Studies indicate a critical role for Nrf2 in maintaining redox balance in the airways against environmental insults.

Conclusions:

• Nrf2 signaling is crucial for protecting the airways from oxidative stress and environmental pollutants.
• Dysregulation or deficiency of Nrf2 contributes to the pathogenesis of numerous respiratory diseases.
• Targeting Nrf2 activation represents a promising therapeutic strategy for managing and treating lung disorders.