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 oxidase, NOX3, oxidative stress, vestibular system, cochlea, hearing loss, molecular biology-based inhibitors, small molecules inhibitors.
Current Pharmaceutical Design
Title:NOX3-Targeted Therapies for Inner Ear Pathologies
Volume: 21 Issue: 41
Author(s): Francis Rousset, Stephanie Carnesecchi, Pascal Senn and Karl-Heinz Krause
Affiliation:
Keywords: NADPH oxidase, NOX3, oxidative stress, vestibular system, cochlea, hearing loss, molecular biology-based inhibitors, small molecules inhibitors.
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.
Export Options
About this article
Cite this article as:
Rousset Francis, Carnesecchi Stephanie, Senn Pascal and Krause Karl-Heinz, NOX3-Targeted Therapies for Inner Ear Pathologies, Current Pharmaceutical Design 2015; 21 (41) . https://dx.doi.org/10.2174/1381612821666151029112421
DOI https://dx.doi.org/10.2174/1381612821666151029112421 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Pan-Cancer Review of <i>ALK</i> Mutations: Implications for Carcinogenesis and Therapy
Current Cancer Drug Targets Elucidation of PLK1 Linked Biomarkers in Oesophageal Cancer Cell Lines: A Step Towards Novel Signaling Pathways by p53 and PLK1-Linked Functions Crosstalk
Protein & Peptide Letters Targeting the EGFR-family for Therapy: Biological Challenges and Clinical Perspective
Current Pharmaceutical Design microRNA-133: Expression, Function and Therapeutic Potential in Muscle Diseases and Cancer
Current Drug Targets The Role of HTS in Drug Discovery at the University of Michigan
Combinatorial Chemistry & High Throughput Screening Analysis of Current Antifungal Agents and Their Targets within the Pneumocystis carinii Genome
Current Drug Targets Metal Complexes, their Cellular Targets and Potential for Cancer Therapy
Current Pharmaceutical Design A New Antitumor Agent, (3-chloro-7-methoxyfuro[2,3-b]-quinolin-4-yl)-(4-methoxyphenyl) amine, Loaded in Solid Lipid Nanoparticles: Characterization and Pharmacokinetics
Current Nanoscience Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation
Current Stem Cell Research & Therapy miRNA and Proteomic Dysregulation in Non-Small Cell Lung Cancer in Response to Cigarette Smoke
MicroRNA Hypoxia in Du-145 Prostate Cancer Xenografts After Estramustine Phosphate and Radiotherapy
Current Radiopharmaceuticals Liposomes as Nanovaccine Delivery Systems
Current Topics in Medicinal Chemistry Salinomycin Suppresses Tumorigenicity of Liver Cancer Stem Cells and Wnt/Beta-catenin Signaling
Current Stem Cell Research & Therapy Cancer Immunotherapy: Battling Tumors with Gene Vaccines
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Accuracy of a Topical PET/CT Scanner on SUV Measurements of Small Volumes SUV
Current Medical Imaging Targeting p73 - a Potential Approach in Cancer Treatment
Current Pharmaceutical Design Radiochemotherapy for Non Small Cell Lung Cancer
Current Drug Therapy Curcumin and its Formulations: Potential Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Molecular Imaging of Neuropsychiatry and Boron Neutron Capture Therapy in Neuro-oncology
Current Molecular Imaging (Discontinued) Objective Biomarkers or Symptom Scores for the Classification of Fibromyalgia Syndrome?
Current Rheumatology Reviews