NADPH oxidase isoform (NOX)

NADPH oxidase isoforms are a family of membrane-bound enzymes whose main function is to catalyze the production of reactive oxygen species by transferring electrons from NADPH to molecular oxygen. Seven isoforms are present in humans: NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Each isoform differs in activation mechanisms, subunit composition, tissue distribution, and regulatory properties, but all share a core domain structure involving electron transport across cellular membranes. These enzymes critically regulate oxidative stress, immune defense, cellular signaling, and can mediate both protective and pathological roles, particularly in inflammation, cardiovascular, neurodegenerative diseases, cancer, and fibrotic disorders. Several drugs have been developed to target specific NOX isoforms due to their involvement in human disease, but isoform selectivity and preservation of essential ROS-mediated signaling remain major therapeutic challenges.

Other names

NADPH oxidaseNOX (with isoform prefixes, e.g. NOX2, NOX4)respiratory burst oxidase homolog (RBOH, mainly in plant biology)

Direct inhibition of electron transport activity: blocking FAD or heme domains to prevent ROS formation; Blocking subunit assembly (for those isoforms requiring cytosolic subunit interactions, e.g. NOX2); Calcium-dependent inhibitor action (for NOX5 and DUOX1/2)