NOX enzymes as novel targets for drug development

J. David Lambeth, Karl Heinz Krause, Robert A Clark

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

The members of the NOX/DUOX family of NADPH oxidases mediate such physiologic functions as host defense, cell signaling, and thyroid hormone biosynthesis through the generation of reactive oxygen species (ROS), including superoxide anion and hydrogen peroxide. Moreover, ROS are involved in a broad range of fundamental biochemical and cellular processes, and data accumulated in recent years indicate that the NOX enzymes comprise one of the most important biological sources of ROS. Given the high biochemical reactivity of ROS, it is not surprising that they have been implicated in a wide variety of pathologies and diseases. Prominent among the settings that feature ROS-mediated tissue injury are disorders associated with inflammation, aging, and progressive degenerative changes in cells and organ systems, and it appears that essentially no organ system is exempt. Among the disorders currently believed to be mediated at least in part by NOX-derived ROS are hypertension, aortic aneurysm, myocardial infarction (and other ischemia-reperfusion disorders), pulmonary fibrosis and hypertension, amyotropic lateral sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, diabetic nephropathy, and renal cell carcinoma. Several small-molecule and peptide inhibitors of the NOX enzymes have been useful in experimental studies, but issues of specificity, potency, and toxicity militate against any of the existing published compounds as candidates for drug development. Given the broad array of disease targets documented in recent work, the time is here for vigorous efforts to develop clinically useful inhibitors of the NOX enzymes. As most (though not all) NOX-related diseases appear to be mediated by a single member of the NOX family, agents with isoform specificity will be preferred, although broadly active NOX inhibitors may prove to be useful in some settings.

Original languageEnglish (US)
Pages (from-to)339-363
Number of pages25
JournalSeminars in Immunopathology
Volume30
Issue number3
DOIs
StatePublished - Jul 2008

Fingerprint

Reactive Oxygen Species
Enzymes
Pharmaceutical Preparations
Enzyme Inhibitors
Biochemical Phenomena
Motor Neuron Disease
Pulmonary Fibrosis
Aortic Aneurysm
NADPH Oxidase
Diabetic Nephropathies
Thyroid Hormones
Renal Cell Carcinoma
Pulmonary Hypertension
Superoxides
Hydrogen Peroxide
Reperfusion
Parkinson Disease
Alzheimer Disease
Protein Isoforms
Ischemia

Keywords

  • Drug development
  • Nox
  • Reactive oxygen

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

NOX enzymes as novel targets for drug development. / Lambeth, J. David; Krause, Karl Heinz; Clark, Robert A.

In: Seminars in Immunopathology, Vol. 30, No. 3, 07.2008, p. 339-363.

Research output: Contribution to journalArticle

Lambeth, J. David ; Krause, Karl Heinz ; Clark, Robert A. / NOX enzymes as novel targets for drug development. In: Seminars in Immunopathology. 2008 ; Vol. 30, No. 3. pp. 339-363.
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