Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy

The coordinating role of nuclear factor erythroid-2-related factor 2 (Nrf2) in cellular function is undeniable. Evidence indicates that this transcription factor exerts massive regulatory functions in multiple signaling pathways concerning redox homeostasis and xenobiotics, macromolecules, and iron metabolism. Being the master regulator of antioxidant system, Nrf2 controls cellular fate, influencing cell proliferation, differentiation, apoptosis, resistance to therapy, and senescence processes, as well as infection disease success. Because Nrf2 is the key coordinator of cell defence mechanisms, dysregulation of its signaling has been associated with carcinogenic phenomena and infectious and age-related diseases. Deregulation of this cytoprotective system may also interfere with immune response. Oxidative burst, one of the main microbicidal mechanisms, could be impaired during the initial phagocytosis of pathogens, which could lead to the successful establishment of infection and promote susceptibility to infectious diseases. There is still a knowledge gap to fill regarding the molecular mechanisms by which Nrf2 orchestrates such complex networks involving multiple pathways. This review describes the role of Nrf2 in non-pathogenic and pathogenic cells.

Automated summary

The coordinating role of nuclear factor erythroid-2-related factor 2 (Nrf2) in cellular function is undeniable. Evidence indicates that Nrf2 exerts regulatory functions in multiple signaling pathways concerning redox homeostasis, xenobiotics, macromolecules, and iron metabolism. Dysregulation of Nrf2 signaling has been associated with carcinogenic phenomena, infectious diseases, and age-related diseases. Further understanding of the molecular mechanisms involved in Nrf2's coordination of complex networks is needed.