title: The complexity of the Nrf2 pathway: beyond the antioxidant response.
abstract: The NF-E2-related factor 2 (Nrf2)-mediated signalling pathway provides living organisms an efficient and pivotal line of defensive to counteract environmental insults and endogenous stressors. Nrf2 coordinates the basal and inducible expression of antioxidant and Phase II detoxification enzymes to adapt to different stress conditions. The stability and cellular distribution of Nrf2 is tightly controlled by its inhibitory binding protein Kelch-like ECH-associated protein 1. Nrf2 signalling is also regulated by posttranslational, transcriptional, translational and epigenetic mechanisms, as well as by other protein partners, including p62, p21 and IQ motif-containing GTPase activating protein 1. Many studies have demonstrated that Nrf2 is a promising target for preventing carcinogenesis and other chronic diseases, including cardiovascular diseases, neurodegenerative diseases and pulmonary injury. However, constitutive activation of Nrf2 in advanced cancer cells may confer drug resistance. Here, we review the molecular mechanisms of Nrf2 signalling, the diverse classes of Nrf2 activators, including bioactive nutrients and other chemicals, and the cellular functions and disease relevance of Nrf2 and discuss the dual role of Nrf2 in different contexts.
authors.affiliation: Department of Pharmaceutics, Earnest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutics, Earnest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Wenji
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Earnest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Zheng-yuan
authors.initials: ZY
authors.lastname: Su
authors.affiliation: Department of Pharmaceutics, Earnest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Electronic address: KongT@pharmacy.rutgers.edu.
authors.forename: Ah-Ng Tony
authors.initials: AN
authors.lastname: Kong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000502:physiology; D002908:Chronic Disease; D004351:Drug Resistance; D044127:Epigenesis, Genetic; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013312:Stress, Physiological; D015262:Xenobiotics
chemical_list: D000975:Antioxidants; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D015262:Xenobiotics; D020558:GTP Phosphohydrolases
keywords: Activator; Antioxidant; Kelch-like ECH-associated protein 1 (Keap1); NF-E2-related factor 2 (Nrf2); Nutrients; ROS