The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic

Maria A. O'Connell (Lead / Corresponding author), John D. Hayes

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    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.

    Original languageEnglish
    Pages (from-to)687-689
    Number of pages3
    JournalBiochemical Society Transactions
    Issue number4
    Early online date3 Aug 2015
    Publication statusPublished - Aug 2015


    • Cytoprotection
    • Kelch-like ECH-associated protein-1 (Keap1)
    • Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)
    • Redox
    • Signalling
    • Stress


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