Cytochrome b-245 beta chain (NOX2) (NOX2)

Cytochrome b-245 beta chain, commonly known as NOX2 or gp91phox, is the catalytic, membrane-spanning subunit of the phagocyte NADPH oxidase complex [1, 4, 6]. Its primary biological function is to transfer electrons from NADPH to molecular oxygen, generating superoxide radicals and other reactive oxygen species (ROS) essential for the microbicidal activity of phagocytes like neutrophils and macrophages [5, 9, 10]. Mutations in the CYBB gene, which encodes this protein, lead to X-linked Chronic Granulomatous Disease (CGD), a condition characterized by a severely compromised immune system and recurrent life-threatening infections [1, 5, 14]. Conversely, excessive NOX2 activity and the resulting oxidative stress are implicated in the pathogenesis of various chronic conditions, including atherosclerosis, hypertension, neurodegenerative diseases, and chronic inflammation [3, 6, 9]. Consequently, NOX2 has emerged as a significant therapeutic target, with small-molecule inhibitors like GSK2795039 being developed to mitigate oxidative damage in these diseases [3, 7, 9]. However, therapeutic inhibition of NOX2 carries the risk of inducing a transient CGD-like state, potentially increasing patient susceptibility to infections [3, 10].

Other names

CYBBgp91phoxgp91-phoxp91-PHOXNADPH oxidase 2Cytochrome b-245 heavy chainCytochrome b558 subunit betaSuperoxide-generating NADPH oxidase heavy chain subunitHeme-binding membrane glycoprotein gp91phox

Inhibition of the NADPH oxidase complex to prevent the transfer of electrons from NADPH to molecular oxygen, thereby reducing the production of superoxide and other reactive oxygen species (ROS).