title: The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic.
abstract: The transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, with gene called NFE2L2) is a master regulator of the antioxidant response. In the last decade, interest has intensified in this research area as its importance in several physiological and pathological processes has become widely recognized; these include redox signalling and redox homoeostasis, drug metabolism and disposition, intermediary metabolism, cellular adaptation to stress, chemoprevention and chemoresistance, toxicity, inflammation, neurodegeneration, lipogenesis and aging. Regulation of Nrf2 is complex and although much attention has focussed on its repression by Kelch-like ECH-associated protein-1 (Keap1), recently it has become increasingly apparent that it is also controlled by cross-talk with other signalling pathways including the glycogen synthase kinase-3 (GSK-3)-β-transducin repeat-containing protein (β-TrCP) axis, ERAD (endoplasmic reticulum-associated degradation)-associated E3 ubiquitin-protein ligase (Hrd1, also called synoviolin), nuclear factor-kappa B (NF-κB), Notch and AMP kinase. Due to its beneficial role in several diseases, Nrf2 has become a major therapeutic target, with novel natural, synthetic and targeted small molecules currently under investigation to modulate the pathway and in clinical trials.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, U.K. m.oconnell@uea.ac.uk.
authors.forename: Maria A
authors.initials: MA
authors.lastname: O'Connell
authors.affiliation: Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, U.K.
authors.forename: John D
authors.initials: JD
authors.lastname: Hayes
mesh_terms: D000818:Animals; D003226:Congresses as Topic; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human
keywords: Kelch-like ECH-associated protein-1 (Keap1); cytoprotection; nuclear factor-erythroid 2 p45-related factor 2 (Nrf2); redox; signalling; stress