Nuclear factor erythroid 2-related factor 2 – heme oxygenase 1 signaling pathway (Nrf2–HO-1 pathway)

The **Nuclear factor erythroid 2-related factor 2 – heme oxygenase 1 (Nrf2–HO-1) signaling pathway** is a major cellular protective axis against oxidative stress and toxic insults. Nrf2 is a redox-sensitive transcription factor that, under stress conditions, escapes inhibition by Keap1 and translocates to the nucleus to upregulate antioxidant and detoxifying genes, including the inducible enzyme heme oxygenase 1 (HO-1, encoded by HMOX1)[3][7]. HO-1 catalyzes the breakdown of heme, producing biliverdin, bilirubin, carbon monoxide, and iron, conferring cytoprotective, anti-inflammatory, anti-apoptotic, and pro-survival effects[7]. The pathway is implicated in numerous physiological and pathological contexts: it protects against neurodegeneration, liver and cardiovascular diseases, and aging-related oxidative stress, while its dysregulation can contribute to cancer progression, chemoresistance, and maladaptive tissue repair[1][2][5][7][8]. Both pharmacological activation and inhibition of Nrf2/HO-1 have been explored for disease intervention, but the effects are highly context-dependent—therapeutic manipulation requires careful consideration of tissue, disease stage, and potential side-effects[1][2][8].

Other names

Nrf2/HO-1 axisNrf2-HMOX1 pathwayNrf2–heme oxygenase 1 pathway

Activation of Nrf2 to induce antioxidant and cytoprotective genes (including HO-1)[5][7] Inhibition of Nrf2 to downregulate angiogenesis and cell survival in cancer[2] Inhibition of HO-1 to reduce pathological bilirubin and iron accumulation in liver disease[8]