Nicotinamide adenine dinucleotide phosphate oxidase (NOX) (NOX)

The Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family consists of seven transmembrane enzymes (NOX1-5, DUOX1-2) that catalyze the transfer of electrons from NADPH to molecular oxygen to generate reactive oxygen species (ROS) (Bedard & Krause, 2007). Unlike most other enzymes where ROS are metabolic byproducts, NOX enzymes are unique because ROS production is their primary and intentional physiological function (Lambeth, 2004). These enzymes play critical roles in innate immunity, particularly the NOX2-mediated respiratory burst in phagocytes used to destroy invading pathogens, as well as in non-phagocytic cell signaling, gene expression, and regulation of vascular tone (Brandes et al., 2010). Chronic overactivation of NOX isoforms is a central driver of oxidative stress, which contributes to the progression of cardiovascular diseases, chronic kidney disease, neurodegeneration, and various fibrotic conditions (Vermot et al., 2021). Conversely, genetic deficiency in NOX2 leads to Chronic Granulomatous Disease, a severe primary immunodeficiency characterized by recurrent life-threatening infections (Meitzler et al., 2014). Therapeutic development focuses on isoform-selective inhibitors, such as Setanaxib (GKT137831), which targets NOX1 and NOX4 to treat primary biliary cholangitis and Alport syndrome without compromising the immune functions of NOX2 (Calliditas Therapeutics, 2023). Monitoring NOX activity in clinical settings often involves measuring biomarkers of oxidative damage, such as nitrotyrosine or malondialdehyde, or direct ROS production in isolated cells (Altenhöfer et al., 2015).

Other names

NADPH oxidase familyNOX enzymesRespiratory burst oxidaseDUOXDual oxidaseNicotinamide adenine dinucleotide phosphate-oxidase

Inhibition of the catalytic activity of NOX isoforms to reduce the production of superoxide and hydrogen peroxide, thereby mitigating oxidative stress and downstream pro-inflammatory signaling.