Adverse Effects of Nrf2 in Different Organs and the Related Diseases.

Significance: Under normal physiological conditions, Nrf2 undergoes ubiquitination and subsequent proteasome degradation to maintain its basal activity. Oxidative stress can trigger Nrf2 activation, prompting its translocation to the nucleus where it functions as a transcription factor, activating various antioxidant pathways, and conferring antioxidant properties. Recent Advances: While extensive research has shown Nrf2's protective role in various diseases, emerging evidence suggests that Nrf2 activation can also produce harmful effects. Critical Issues: This review examines the pathological contexts in which Nrf2 assumes different roles, emphasizing the mechanisms and conditions that result in adverse outcomes. Future Directions: Persistent Nrf2 activation may have deleterious consequences, necessitating further investigation into the specific conditions and mechanisms through which Nrf2 exerts its harmful effects. Antioxid. Redox Signal. 00, 000-000.