Gamble Madison E, Sureshkumar Sruthi, Carrera Espinoza Maria Janina, Hakim Natalie L, Espitia Claudia M, Bi Fangchao, Kelly Kevin R, Wang Wei, Nawrocki Steffan T, Carew Jennifer S
Department of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USA.
Department of Pharmacology and Toxicology, University of Arizona College of Pharmacy, Tucson, AZ 85721, USA.
Cells. 2025 Jul 8;14(14):1043. doi: 10.3390/cells14141043.
The NADPH oxidase 2 (NOX2) complex is a critical regulator of immune homeostasis. It is utilized by phagocytic leukocytes including neutrophils, monocytes, and macrophages to generate reactive oxygen species (ROS) that drive microbe clearance and modulate inflammatory responses. Within NOX2, the essential scaffold protein p47phox plays a pivotal role in orchestrating enzyme activation and facilitating the assembly and membrane translocation of cytosolic components of the complex. Tight regulation of p47phox activity is crucial, and its disruption is linked to a number of pathological conditions. Conversely, its hyperactivity contributes to oxidative stress, tissue damage, the progression of cardiovascular diseases, neurodegenerative disorders, inflammatory conditions, metabolic syndromes, and cancer. In this review, we detail the structural and functional roles of p47phox, mechanisms of its regulation, and its multifaceted contributions to disease pathogenesis. We explore the latest advances in p47phox-targeted therapeutic strategies, discuss current challenges in the field, highlight p47phox's potential as a transformative target in redox biology and propose future directions to unlock its clinical utility.
NADPH氧化酶2（NOX2）复合物是免疫稳态的关键调节因子。包括中性粒细胞、单核细胞和巨噬细胞在内的吞噬性白细胞利用它产生活性氧（ROS），以促进微生物清除并调节炎症反应。在NOX2中，关键的支架蛋白p47phox在协调酶激活以及促进复合物胞质成分的组装和膜易位方面发挥着关键作用。对p47phox活性的严格调控至关重要，其功能紊乱与多种病理状况相关。相反，其过度活跃会导致氧化应激、组织损伤、心血管疾病进展、神经退行性疾病、炎症性疾病、代谢综合征和癌症。在本综述中，我们详细阐述了p47phox的结构和功能作用、其调控机制以及它对疾病发病机制的多方面贡献。我们探讨了针对p47phox的治疗策略的最新进展，讨论了该领域当前面临的挑战，强调了p47phox作为氧化还原生物学中变革性靶点的潜力，并提出了释放其临床应用价值的未来方向。
