Kelch-like ECH-associated protein 1–Nuclear factor erythroid 2–related factor 2 pathway (Keap1–Nrf2 pathway)

The Kelch-like ECH-associated protein 1–Nuclear factor erythroid 2–related factor 2 pathway, commonly known as the Keap1–Nrf2 pathway, is a central cellular defense mechanism against oxidative and electrophilic stress. Under normal conditions, Keap1 binds to Nrf2 in the cytosol and targets it for proteasomal degradation. Upon exposure to oxidative or electrophilic stress, Keap1 undergoes conformational changes leading to the release and stabilization of Nrf2. Stabilized Nrf2 translocates to the nucleus, where it heterodimerizes with small Maf proteins and binds to antioxidant response elements (AREs) in the promoters of cytoprotective genes, activating their transcription. These genes mediate antioxidant production, detoxification, and maintenance of redox homeostasis. The pathway is implicated in diverse physiological and pathological processes, including carcinogenesis, neuroprotection, and chronic inflammatory disease. Therapeutically, both inhibition and activation of this pathway are under investigation, but excessive Nrf2 activation can contribute to cancer progression and resistance to chemotherapy[1][2][5][6]. The name provided in the query combines a protein complex (Keap1–Nrf2) with a downstream DNA element (ARE, antioxidant response element). For most structured biological use, the canonical target is usually defined as “Kelch-like ECH-associated protein 1–Nuclear factor erythroid 2–related factor 2 pathway” or simply “Keap1–Nrf2 pathway.” The current query’s combination is overly broad and merges pathway (Keap1–Nrf2) with gene elements (ARE) and would be marked as is_incorrect: true for canonical drug target mapping[1][2][5].

Other names

Keap1–Nfe2l2 pathwayKeap1–Nrf2–ARE pathwayNrf2 pathwayNFE2L2 pathway

Activation (agonism) of Nrf2, Inhibition of Keap1-mediated Nrf2 degradation, Induction of antioxidant response element (ARE)-driven genes