Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multisubunit enzyme complex that participates in the generation of superoxide or hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and plays a key role in several biological functions. Among seven known NOX i...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/2/429 |
| _version_ | 1797622734128152576 |
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| author | Cristina Nocella Alessandra D’Amico Vittoria Cammisotto Simona Bartimoccia Valentina Castellani Lorenzo Loffredo Leonardo Marini Giulia Ferrara Matteo Testa Giulio Motta Beatrice Benazzi Fabio Zara Giacomo Frati Sebastiano Sciarretta Pasquale Pignatelli Francesco Violi Roberto Carnevale Smile Group |
| author_facet | Cristina Nocella Alessandra D’Amico Vittoria Cammisotto Simona Bartimoccia Valentina Castellani Lorenzo Loffredo Leonardo Marini Giulia Ferrara Matteo Testa Giulio Motta Beatrice Benazzi Fabio Zara Giacomo Frati Sebastiano Sciarretta Pasquale Pignatelli Francesco Violi Roberto Carnevale Smile Group |
| author_sort | Cristina Nocella |
| collection | DOAJ |
| description | Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multisubunit enzyme complex that participates in the generation of superoxide or hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and plays a key role in several biological functions. Among seven known NOX isoforms, NOX2 was the first identified in phagocytes but is also expressed in several other cell types including endothelial cells, platelets, microglia, neurons, and muscle cells. NOX2 has been assigned multiple roles in regulating many aspects of innate and adaptive immunity, and human and mouse models of NOX2 genetic deletion highlighted this key role. On the other side, NOX2 hyperactivation is involved in the pathogenesis of several diseases with different etiologies but all are characterized by an increase in oxidative stress and inflammatory process. From this point of view, the modulation of NOX2 represents an important therapeutic strategy aimed at reducing the damage associated with its hyperactivation. Although pharmacological strategies to selectively modulate NOX2 are implemented thanks to new biotechnologies, this field of research remains to be explored. Therefore, in this review, we analyzed the role of NOX2 at the crossroads between immunity and pathologies mediated by its hyperactivation. We described (1) the mechanisms of activation and regulation, (2) human, mouse, and cellular models studied to understand the role of NOX2 as an enzyme of innate immunity, (3) some of the pathologies associated with its hyperactivation, and (4) the inhibitory strategies, with reference to the most recent discoveries. |
| first_indexed | 2024-03-11T09:14:27Z |
| format | Article |
| id | doaj.art-db7b39be6fe742508f9b402b38f296f6 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:27Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-db7b39be6fe742508f9b402b38f296f62023-11-16T18:48:05ZengMDPI AGAntioxidants2076-39212023-02-0112242910.3390/antiox12020429Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated PathologiesCristina Nocella0Alessandra D’Amico1Vittoria Cammisotto2Simona Bartimoccia3Valentina Castellani4Lorenzo Loffredo5Leonardo Marini6Giulia Ferrara7Matteo Testa8Giulio Motta9Beatrice Benazzi10Fabio Zara11Giacomo Frati12Sebastiano Sciarretta13Pasquale Pignatelli14Francesco Violi15Roberto Carnevale16Smile Group17Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, ItalyDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of General and Specialistic Surgery “Paride Stefanini”, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, ItalyDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, ItalyFaculty of Medicine and Surgery, Course E, Sapienza University of Rome, 04100 Latina, ItalyNicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multisubunit enzyme complex that participates in the generation of superoxide or hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and plays a key role in several biological functions. Among seven known NOX isoforms, NOX2 was the first identified in phagocytes but is also expressed in several other cell types including endothelial cells, platelets, microglia, neurons, and muscle cells. NOX2 has been assigned multiple roles in regulating many aspects of innate and adaptive immunity, and human and mouse models of NOX2 genetic deletion highlighted this key role. On the other side, NOX2 hyperactivation is involved in the pathogenesis of several diseases with different etiologies but all are characterized by an increase in oxidative stress and inflammatory process. From this point of view, the modulation of NOX2 represents an important therapeutic strategy aimed at reducing the damage associated with its hyperactivation. Although pharmacological strategies to selectively modulate NOX2 are implemented thanks to new biotechnologies, this field of research remains to be explored. Therefore, in this review, we analyzed the role of NOX2 at the crossroads between immunity and pathologies mediated by its hyperactivation. We described (1) the mechanisms of activation and regulation, (2) human, mouse, and cellular models studied to understand the role of NOX2 as an enzyme of innate immunity, (3) some of the pathologies associated with its hyperactivation, and (4) the inhibitory strategies, with reference to the most recent discoveries.https://www.mdpi.com/2076-3921/12/2/429NOX2oxidative stressinflammationimmunitytherapeutics |
| spellingShingle | Cristina Nocella Alessandra D’Amico Vittoria Cammisotto Simona Bartimoccia Valentina Castellani Lorenzo Loffredo Leonardo Marini Giulia Ferrara Matteo Testa Giulio Motta Beatrice Benazzi Fabio Zara Giacomo Frati Sebastiano Sciarretta Pasquale Pignatelli Francesco Violi Roberto Carnevale Smile Group Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies Antioxidants NOX2 oxidative stress inflammation immunity therapeutics |
| title | Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies |
| title_full | Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies |
| title_fullStr | Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies |
| title_full_unstemmed | Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies |
| title_short | Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies |
| title_sort | structure activation and regulation of nox2 at the crossroad between the innate immunity and oxidative stress mediated pathologies |
| topic | NOX2 oxidative stress inflammation immunity therapeutics |
| url | https://www.mdpi.com/2076-3921/12/2/429 |
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