From Defense to Disease: NADPH Oxidase in Cellular Function and Dysregulation.

Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase is an important family of enzymes that produce reactive oxygen species (ROS) and consists of NOX1-5, DUOX1, and DUOX2. These enzymes exhibit diverse tissue distributions with different activation mechanisms involved. They play vital roles in several physiological processes, such as defense against pathogens, wound healing, regulation of gene expression, post-translational modification of proteins, cell signaling, and cell differentiation. The present review highlights an indispensable role of NOX expression and resulting ROS production on various biological processes, specifically focusing on cell differentiation at various stages of embryonic development and differentiation of monocytes to macrophages within the mononuclear phagocytic system. It also discusses the influence of altered expression of NOX isoforms on the fate of macrophage polarization either towards pro-inflammatory (M1) or anti-inflammatory (M2) macrophages. Additionally, it discusses how the dysregulation of the cellular expression of NOXs is involved in the development and progression of a variety of chronic human diseases including cardiovascular diseases, cancer, diabetes, neurological diseases, and autoimmune disorders.