A New Approach to Treating Neurodegenerative Otologic Disorders

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dc.contributor.authorMoos, Walter H.
dc.contributor.authorFaller, Douglas V.
dc.contributor.authorGlavas, Ioannis P.
dc.contributor.authorHarpp, David N.
dc.contributor.authorIrwin, Michael H.
dc.contributor.authorKanara, Iphigenia
dc.contributor.authorPinkert, Carl A.
dc.contributor.authorPowers, Whitney R.
dc.contributor.authorSteliou, Kosta
dc.contributor.authorVavvas, Demetrios G.
dc.contributor.authorKodukula, Krishna
dc.contributor.otherUniversity of California San Francisco
dc.contributor.otherBoston University
dc.contributor.otherNew York University
dc.contributor.otherMcGill University
dc.contributor.otherAuburn University
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherHarvard University
dc.contributor.otherMassachusetts Eye & Ear Infirmary
dc.contributor.otherHarvard Medical School
dc.date.accessioned2023-09-28T19:18:43Z
dc.date.available2023-09-28T19:18:43Z
dc.date.issued2018
dc.description.abstractHearing loss, the most common neurological disorder and the fourth leading cause of years lived with disability, can have profound effects on quality of life. The impact of this invisible disability, with significant consequences, economic and personal, is most substantial in low- and middle-income countries, where >80% of affected people live. Given the importance of hearing for communication, enjoyment, and safety, with up to 500 million affected globally at a cost of nearly $800 billion/year, research on new approaches toward prevention and treatment is attracting increased attention. The consequences of noise pollution are largely preventable, but irreversible hearing loss can result from aging, disease, or drug side effects. Once damage occurs, treatment relies on hearing aids and cochlear implants. Preventing, delaying, or reducing some degree of hearing loss may be possible by avoiding excessive noise and addressing major contributory factors such as cardiovascular risk. However, given the magnitude of the problem, these interventions alone are unlikely to be sufficient. Recent advances in understanding principal mechanisms that govern hearing function, together with new drug discovery paradigms designed to identify efficacious therapies, bode well for pharmaceutical intervention. This review surveys various causes of loss of auditory function and discusses potential neurological underpinnings, including mitochondrial dysfunction. Mitochondria mitigate cell protection, survival, and function and may succumb to cumulative degradation of energy production and performance; the end result is cell death. Energy-demanding neurons and vestibulocochlear hair cells are vulnerable to mitochondrial dysfunction, and hearing impairment and deafness are characteristic of neurodegenerative mitochondrial disease phenotypes. Beyond acting as cellular powerhouses, mitochondria regulate immune responses to infections, and studies of this phenomenon have aided in identifying nuclear factor kappa B and nuclear factor erythroid 2-related factor 2/antioxidant response element signaling as targets for discovery of otologic drugs, respectively, suppressing or upregulating these pathways. Treatment with free radical scavenging antioxidants is one therapeutic approach, with lipoic acid and corresponding carnitine esters exhibiting improved biodistribution and other features showing promise. These compounds are also histone deacetylase (HDAC) inhibitors, adding epigenetic modulation to the mechanistic milieu through which they act. These data suggest that new drugs targeting mitochondrial dysfunction and modulating epigenetic pathways via HDAC inhibition or other mechanisms hold great promise.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationMoos, W. H., Faller, D. V., Glavas, I. P., Harpp, D. N., Irwin, M. H., Kanara, I., Pinkert, C. A., Powers, W. R., Steliou, K., Vavvas, D. G., & Kodukula, K. (2018). A New Approach to Treating Neurodegenerative Otologic Disorders. In BioResearch Open Access (Vol. 7, Issue 1, pp. 107–115). Mary Ann Liebert Inc. https://doi.org/10.1089/biores.2018.0017
dc.identifier.doi10.1089/biores.2018.0017
dc.identifier.orcidhttps://orcid.org/0000-0001-7244-811X
dc.identifier.orcidhttps://orcid.org/0000-0001-7460-3881
dc.identifier.orcidhttps://orcid.org/0000-0002-8622-6478
dc.identifier.urihttps://ir.ua.edu/handle/123456789/11282
dc.languageEnglish
dc.language.isoen_US
dc.publisherMary Ann Liebert
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectcarnitine esters
dc.subjectepigenetics
dc.subjecthearing loss
dc.subjectlipoic acid
dc.subjectmitochondrial dysfunction
dc.subjectpharmaceutical
dc.subjectALPHA-LIPOIC ACID
dc.subjectINDUCED HEARING-LOSS
dc.subjectNF-KAPPA-B
dc.subjectOXIDATIVE STRESS
dc.subjectEPIGENETIC TREATMENT
dc.subjectMITOCHONDRIAL DISEASES
dc.subjectINNER-EAR
dc.subjectCOCHLEAR IMPLANTATION
dc.subjectNOISE EXPOSURE
dc.subjectANIMAL-MODEL
dc.subjectBiochemistry & Molecular Biology
dc.titleA New Approach to Treating Neurodegenerative Otologic Disordersen_US
dc.typeArticle
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