p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases
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 ess...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/14/1043 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849406799013216256 |
|---|---|
| author | Madison E. Gamble Sruthi Sureshkumar Maria Janina Carrera Espinoza Natalie L. Hakim Claudia M. Espitia Fangchao Bi Kevin R. Kelly Wei Wang Steffan T. Nawrocki Jennifer S. Carew |
| author_facet | Madison E. Gamble Sruthi Sureshkumar Maria Janina Carrera Espinoza Natalie L. Hakim Claudia M. Espitia Fangchao Bi Kevin R. Kelly Wei Wang Steffan T. Nawrocki Jennifer S. Carew |
| author_sort | Madison E. Gamble |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-abdb11d93ceb40a0bc731e6b7090529e |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-abdb11d93ceb40a0bc731e6b7090529e2025-08-20T03:36:17ZengMDPI AGCells2073-44092025-07-011414104310.3390/cells14141043p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related DiseasesMadison E. Gamble0Sruthi Sureshkumar1Maria Janina Carrera Espinoza2Natalie L. Hakim3Claudia M. Espitia4Fangchao Bi5Kevin R. Kelly6Wei Wang7Steffan T. Nawrocki8Jennifer S. Carew9Department of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Pharmacology and Toxicology, University of Arizona College of Pharmacy, Tucson, AZ 85721, USADivision of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USADepartment of Pharmacology and Toxicology, University of Arizona College of Pharmacy, Tucson, AZ 85721, USADepartment of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USADepartment of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USAThe 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.https://www.mdpi.com/2073-4409/14/14/1043p47phoxoxidative stressredoxcancertargeted therapy |
| spellingShingle | Madison E. Gamble Sruthi Sureshkumar Maria Janina Carrera Espinoza Natalie L. Hakim Claudia M. Espitia Fangchao Bi Kevin R. Kelly Wei Wang Steffan T. Nawrocki Jennifer S. Carew p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases Cells p47phox oxidative stress redox cancer targeted therapy |
| title | p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases |
| title_full | p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases |
| title_fullStr | p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases |
| title_full_unstemmed | p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases |
| title_short | p47phox: A Central Regulator of NADPH Oxidase Function and a Promising Therapeutic Target in Redox-Related Diseases |
| title_sort | p47phox a central regulator of nadph oxidase function and a promising therapeutic target in redox related diseases |
| topic | p47phox oxidative stress redox cancer targeted therapy |
| url | https://www.mdpi.com/2073-4409/14/14/1043 |
| work_keys_str_mv | AT madisonegamble p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT sruthisureshkumar p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT mariajaninacarreraespinoza p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT natalielhakim p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT claudiamespitia p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT fangchaobi p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT kevinrkelly p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT weiwang p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT steffantnawrocki p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases AT jenniferscarew p47phoxacentralregulatorofnadphoxidasefunctionandapromisingtherapeutictargetinredoxrelateddiseases |