Neutrophil NADPH oxidase (NOX2) (NOX2)

The neutrophil NADPH oxidase, primarily known as the NOX2 complex, is a multicomponent enzyme system essential for the innate immune response through the production of reactive oxygen species (ROS) during the respiratory burst [1, 2]. It consists of the membrane-bound cytochrome b558 (comprising gp91phox and p22phox) and several cytosolic regulatory subunits (p47phox, p67phox, p40phox, and the small GTPase Rac) that translocate to the membrane upon activation [3, 4]. While its primary biological function is the destruction of phagocytosed pathogens, dysregulated or chronic activation of this pathway is a major driver of oxidative stress and tissue damage in inflammatory, cardiovascular, and neurodegenerative diseases [5, 6]. Pharmacological intervention strategies include the use of small molecule inhibitors that target the catalytic activity of the gp91phox subunit or disrupt the protein-protein interactions required for complex assembly [7, 8]. However, therapeutic development is challenged by the need to maintain sufficient host defense, as total loss of NOX2 function leads to Chronic Granulomatous Disease, characterized by severe recurrent infections [9, 10]. Sources: [1] Panday et al. (2015) Front Immunol; [2] Bedard & Krause (2007) Physiol Rev; [3] El-Benna et al. (2009) FEBS J; [4] Lambeth (2004) Nat Rev Immunol; [5] Drummond et al. (2011) Br J Pharmacol; [6] Block (2008) BMC Neurosci; [7] Altenhöfer et al. (2015) Antiox Redox Signal; [8] Hirano et al. (2015) ACS Med Chem Lett; [9] Roos (2016) J Innate Immun; [10] Curnutte (1993) Clin Immunol Immunopathol.

Other names

Phagocyte NADPH oxidasegp91phox complexRespiratory burst oxidaseNADPH oxidase 2Cytochrome b-245Phox

Inhibition of the enzymatic conversion of molecular oxygen to superoxide by blocking electron transfer from NADPH or by preventing the translocation and assembly of cytosolic regulatory subunits (p47phox, p67phox, p40phox) with the membrane-bound catalytic core (gp91phox and p22phox).