Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) (NOX)

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, or the NOX family, consists of seven enzymes (NOX1-5, DUOX1-2) that serve as primary sources of reactive oxygen species (ROS) in various tissues (Bedard & Krause, 2007, Physiological Reviews). Unlike most enzymes that produce ROS as a metabolic byproduct, the sole biological function of NOX enzymes is the intentional generation of superoxide or hydrogen peroxide (Lambeth, 2004, Nature Reviews Immunology). These enzymes are critical for the innate immune system, where NOX2 facilitates the respiratory burst in phagocytes to destroy invading pathogens (Panday et al., 2015, BioMed Research International). Beyond host defense, NOX-derived ROS act as secondary messengers in signaling pathways that regulate cell growth, differentiation, and vascular tone (Drummond et al., 2011, Clinical Science). Pathological overactivation of NOX isoforms is a major driver of oxidative stress, contributing to cardiovascular diseases, chronic kidney disease, and neurodegeneration (Meitzler et al., 2014, Genes). Conversely, genetic deficiencies in NOX components lead to Chronic Granulomatous Disease, characterized by severe recurrent infections (Vermot et al., 2021, Antioxidants). Therapeutic development focuses on isoform-specific inhibitors, such as Setanaxib (GKT137831), which targets NOX1 and NOX4 to treat fibrotic conditions like primary biliary cholangitis (Hecker et al., 2014, Science Translational Medicine). These drugs aim to reduce harmful oxidative stress while maintaining the essential signaling and immune functions of other NOX isoforms.

Other names

NOX familyRespiratory burst oxidaseNADPH:oxygen oxidoreductaseDUOX (Dual oxidase)Cytochrome b-245

Inhibition of reactive oxygen species production by blocking the catalytic transfer of electrons from NADPH to molecular oxygen or preventing the assembly of the multi-subunit enzyme complex.