The NADPH Oxidase Family and its Inhibitors

Kleniewska, Paulina; Piechota, Aleksandra; Skibska, Beata; Gorąca, Anna

doi:10.1007/s00005-012-0176-z

Cited by 119 publications

(110 citation statements)

References 195 publications

(169 reference statements)

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“…The catalytically dormant NOX2 in its membrane complex with p22phox becomes activated as a result of assembly with cytosolic regulatory partner proteins p40phox, p47phox, p67phox, and Rac1/2, a process triggered by phosphorylation of p47phox and probably other components, and by guanine nucleotide exchange on Rac. The structure and function of NOX enzymes has been extensively reviewed (17,141,153,155,287). For the present purpose, we point out that the presence of multiple specialized domains that mediate protein-protein interactions during the assembly process provide, in addition to the NADPH-binding site on NOX2, a number of candidate binding sites through which inhibitors might target the NOX2 system by disrupting assembly.…”

Section: Cellular Sources Of Rosmentioning

confidence: 97%

“…The physiological effects of NOX-generated ROS on various vascular cells, most notably endothelial and vascular smooth muscle cells (VSMCs), have been a focus of intense interest (27,141,159,174,260). Understanding specific roles for NOX2 is complicated by the presence of several NOX family members in vascular cell types, and different isoform expression in different anatomical regions of the vasculature (venous vs. arterial, lung vs. general circulation, microvasculature, etc.…”

Section: Vascular Cellsmentioning

confidence: 99%

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NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

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Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23,

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Section: Cellular Sources Of Rosmentioning

confidence: 97%

Section: Vascular Cellsmentioning

confidence: 99%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

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“…In immune cells such as neutrophils and macrophages, NOX2 (also called gp91phox) is used as a «superoxide gun» to kill pathogens during phagocytosis [30]. In addition to the phagocyte NOX2, six non-phagocytic NOXs have been identified: NOX1, NOX3, NOX4, NOX5, DUOX1 and DUOX2 [31]. Skeletal muscle expressed NOX2 and NOX4, located in the sarcoplasmic reticulum, the sarcolemma and transverse tubules [29,32].…”

Section: Source Of Rons In Skeletal Musclementioning

confidence: 99%

From physical inactivity to immobilization: Dissecting the role of oxidative stress in skeletal muscle insulin resistance and atrophy

Pierre

Appriou

Gratas-Delamarche

et al. 2016

Free Radical Biology and Medicine

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In the literature, the terms physical inactivity and immobilization are largely used as synonyms. The present review emphasizes the need to establish a clear distinction between these two situations. Physical inactivity is a behavior characterized by a lack of physical activity, whereas immobilization is a deprivation of movement for medical purpose. In agreement with these definitions, appropriate models exist to study either physical inactivity or immobilization, leading thereby to distinct conclusions. In this review, we examine the involvement of oxidative stress in skeletal muscle insulin resistance and atrophy induced by, respectively, physical inactivity and immobilization. A large body of evidence demonstrates that immobilization-induced atrophy depends on the chronic overproduction of reactive oxygen and nitrogen species (RONS). On the other hand, the involvement of RONS in physical inactivity-induced insulin resistance has not been investigated. This observation outlines the need to elucidate the mechanism by which physical inactivity promotes insulin resistance.

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“…Nevertheless, a few hold significant promise. Many reviews have been dedicated to describing the available Nox inhibitors in recent years (29,48,78,85,89) and since then relatively few new compounds have come to the forefront. The following discussion is an effort to be as comprehensive and up-to-date on these developments.…”

Section: Development Of Nox Inhibitors (Peptidic Versus Small-moleculmentioning

confidence: 99%

The Quest for Selective Nox Inhibitors and Therapeutics: Challenges, Triumphs and Pitfalls

Cifuentes-Pagano

Meijles

Pagano

2014

Antioxidants & Redox Signaling

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The NADPH Oxidase Family and its Inhibitors

Cited by 119 publications

References 195 publications

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

From physical inactivity to immobilization: Dissecting the role of oxidative stress in skeletal muscle insulin resistance and atrophy

The Quest for Selective Nox Inhibitors and Therapeutics: Challenges, Triumphs and Pitfalls

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