NADPH oxidase inhibitors: a decade of discovery from Nox2ds to HTS.

Cellular and Molecular Life Sciences : CMLS
Eugenia Cifuentes-PaganoPatrick J Pagano

Abstract

NADPH oxidases (Nox) are established as major sources of reactive oxygen species (ROS). Over the past two decades, Nox-derived ROS have emerged as pivotal in the development of myriad diseases involving oxidative stress. In contrast, Nox are also involved in signaling mechanisms necessary for normal cell function. The study of these enzymes in physiological and pathophysiological conditions is made considerably more complex by the discovery of 7 isoforms: Nox1 through 5 as well as Duox1 and 2, each with its own specific cytosolic components, regulatory control mechanisms, subcellular localization and/or tissue distribution. A clear understanding of the role individual isoforms play in a given system is hindered by the lack of isoform-specific inhibitors. In animal models, knockdown or knockout methodologies are providing definitive answers to perplexing questions of the complex interplay of multiple Nox isoforms in cell and tissue signaling. However, the complex structures and interactions of these heteromeric isozymes predict pleiotropic actions of the Nox subunits and thus suppression of these proteins is almost certain to have untoward effects. Thus, as both therapies and pharmacological tools, molecule-based inhibitors cont...Continue Reading

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Citations

Apr 23, 2013·Antioxidants & Redox Signaling·Augusto C Montezano, Rhian M Touyz
Sep 28, 2013·Antioxidants & Redox Signaling·Eugenia Cifuentes-PaganoPatrick J Pagano
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