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dc.contributor.authorMoos, Walter H.en_US
dc.contributor.authorFaller, Douglas V.en_US
dc.contributor.authorGlavas, Ioannis P.en_US
dc.contributor.authorHarpp, David N.en_US
dc.contributor.authorIrwin, Michael H.en_US
dc.contributor.authorKanara, Iphigeniaen_US
dc.contributor.authorPinkert, Carl A.en_US
dc.contributor.authorPowers, Whitney R.en_US
dc.contributor.authorSteliou, Kostaen_US
dc.contributor.authorVavvas, Demetrios G.en_US
dc.contributor.authorKodukula, Krishnaen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2020-04-09T15:02:06Z
dc.date.available2020-04-09T15:02:06Z
dc.date.issued2018
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30069423
dc.identifier.citationWalter H. Moos, Douglas V. Faller, Ioannis P. Glavas, David N. Harpp, Michael H. Irwin, Iphigenia Kanara, Carl A. Pinkert, Whitney R. Powers, Kosta Steliou, Demetrios G. Vavvas, Krishna Kodukula. 2018. "A New Approach to Treating Neurodegenerative Otologic Disorders.." Biores Open Access, Volume 7, Issue 1, pp. 107 - 115. https://doi.org/10.1089/biores.2018.0017
dc.identifier.issn2164-7844
dc.identifier.urihttps://hdl.handle.net/2144/40072
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.extentpp. 107 - 115en_US
dc.languageEnglish
dc.language.isoen_US
dc.relation.ispartofBioresearch Open Access
dc.rightsCopyright Walter H. Moos et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/.
dc.subjectCarnitine estersen_US
dc.subjectEpigeneticsen_US
dc.subjectHearing lossen_US
dc.subjectLipoic aciden_US
dc.subjectMitochondrial dysfunctionen_US
dc.subjectPharmaceuticalen_US
dc.titleA new approach to treating neurodegenerative otologic disordersen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1089/biores.2018.0017
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, Administrationen_US
pubs.organisational-groupBoston University, School of Medicineen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.orcid0000-0002-5530-3194 (Steliou, Kosta)
dc.identifier.mycv396514


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Copyright Walter H. Moos et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright Walter H. Moos et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.