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NOX3-Targeted therapies for inner ear pathologies

Published in Current pharmaceutical design. 2015, vol. 21, no. 41, p. 5977-5987
Abstract Inner ear pathologies are associated with major morbidity and loss of life quality in affected patients. In many of these conditions, production of reactive oxygen-species (ROS) is thought to be a key pathological mechanism. While the sources of ROS are complex (including for example mitochondria), there is increasing evidence that activation of NOX enzymes, in particular NOX3, plays a key role. NOX3 is a multi-subunit NADPH oxidase, functionally and structurally closely related to NOX1 and NOX2. In both the vestibular and the cochlear compartments of the inner ear, high levels of NOX3 mRNA are expressed. In NOX3 mutant mice, the vestibular function is perturbed due to a lack of otoconia, while only minor alterations of hearing have been documented. However, there is increasing evidence that activation of NOX3 through drugs, noise and probably also aging, leads to hearing loss. Thus, NOX3 is an interesting target to treat and prevent inner ear pathologies and a few first animal models based on drug - or molecular therapy have been reported. So far however, there are no specific NOX3 inhibitors with a documented penetration into the inner ear. Nevertheless, certain antioxidants and non-specific NOX inhibitors diminish hearing loss in animal models. Development of small molecules inhibitors or molecular strategies against NOX3 could improve specificity and efficiency of redox-targeted treatments. In this review, we will discuss arguments for the involvement of NOX3 in inner ear pathologies and therapeutic approaches to target NOX3 activity.
Keywords NADPH oxidaseNOX3Oxidative stressVestibular systemCochleaHearing lossMolecular biology-based inhibitorsSmall molecules inhibitors
PMID: 26510434
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Research groups Groupe Pascal Senn (954)
Radicaux libres et cellules souches embryonnaires (60)
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ROUSSET, Francis et al. NOX3-Targeted therapies for inner ear pathologies. In: Current pharmaceutical design, 2015, vol. 21, n° 41, p. 5977-5987. doi: 10.2174/1381612821666151029112421 https://archive-ouverte.unige.ch/unige:87950

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Deposited on : 2016-10-04

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