The Keap1-Nrf2 cell defense pathway--a promising therapeutic target?

By regulating the basal and inducible expression of an abundance of detoxification enzymes, antioxidant proteins, xenobiotic transporters and other stress response proteins, the Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of mammalian cells to chemical and oxidative insults that have the capacity to provoke cellular harm. This review highlights historical and recent advances in our understanding of the molecular mechanisms that regulate the activity of the Keap1-Nrf2 pathway. The important role of Nrf2 in protecting against the onset of specific diseases and drug-induced toxicities is also examined, alongside the emerging role of Nrf2 in promoting oncogenesis and chemotherapeutic drug resistance. A particular emphasis is placed on the potential for translation of this mechanistic understanding into clinical strategies that can improve human health, with consideration of the potential applications of targeting Nrf2 therapeutically.