Targeting nadph oxidase as a therapeutic strategy for inflammatory diseases

Abstract

Phagocytes produce reactive oxygen species (ROS) through NADPH oxidase (NOX), or respiratory burst oxidase, which play an essential role in the progression of inflammatory disorders. NOX is composed of a membrane-associated heterodimer (flavocytochromeb558, consisting of subunits gp91phox/NOX2 and p22phox), and four cytosolic components (p47phox, p67phox, p40phox and Rac1/2). A growing body of work suggests that peptide-based inhibitors are the most promising candidates for diseases associated with oxidative stress, provided that the target sequence is specific for a particular phagocyte NOX component; therefore, efficacious, well-characterized, and isoform-specific NOX inhibitors might have therapeutic value. We reviewed the peptides that correspond, to domains in gp91phox, p22phox, p47phox, and Rac1/2, and inhibit oxidase activation in vitro and in vivo. Peptide-mimetic compounds and biomaterialconjugates are a drug delivery platform that can enhance the efficacy of active pharmaceutical peptides in vivo. The current review compiles past and current research in the area of inflammation with particular emphasis on peptide-based pharmacological inhibitors derived from gp91phox, p22phoxand p47phox that are involved in the interactions of individual NOX subunits.