Journal article
Using Sox2 to alleviate the hallmarks of age-related hearing loss
Ageing research reviews, Vol.59, pp.101042-101042
05/2020
DOI: 10.1016/j.arr.2020.101042
PMID: 32173536
Abstract
This image presents the new treatment concept proposed in our review: using artificial gene networks that generate an oscillation between activator and repressor to drive the expression of the pluripotency inducing transcription factor, Sox2. This construct is small enough to fit into viral vectors selected to target and express the construct in ‘flat epithelium’ cells that have stably replaced the degenerated organ of Corti, the mammalian hearing organ. Sox2 serves as an activator to drive, alone or in combination with a delayed upregulation of Atoh1, the restoration of a hearing organ out of the flat epithelium.
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Age-related hearing loss (ARHL) is the most prevalent sensory deficit. ARHL reduces the quality of life of the growing population, setting seniors up for the enhanced mental decline. The size of the needy population, the structural deficit, and a likely research strategy for effective treatment of chronic neurosensory hearing in the elderly are needed. Although there has been profound advancement in auditory regenerative research, there remain multiple challenges to restore hearing loss. Thus, additional investigations are required, using novel tools. We propose how the (1) flat epithelium, remaining after the organ of Corti has deteriorated, can be converted to the repaired-sensory epithelium, using Sox2. This will include (2) developing an artificial gene regulatory network transmitted by (3) large viral vectors to the flat epithelium to stimulate remnants of the organ of Corti to restore hair cells. We hope to unite with our proposal toward the common goal, eventually restoring a functional human hearing organ by transforming the flat epithelial cells left after the organ of Corti loss.
Details
- Title: Subtitle
- Using Sox2 to alleviate the hallmarks of age-related hearing loss
- Creators
- Ebenezer N Yamoah - Department of Physiology and Cell Biology, University of Nevada, Reno, USAMark Li - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, USAAnit Shah - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, USAKaren L Elliott - Department of Biology, CLAS, University of Iowa, Iowa City, USAKathy Cheah - Department of Biochemistry, Hong Kong University, Hong Kong, ChinaPin-Xian Xu - Department of Biochemistry, Hong Kong University, Hong Kong, ChinaStacia Phillips - Department of Biochemistry, Hong Kong University, Hong Kong, ChinaSamuel M Young - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, USADaniel F Eberl - Department of Biology, CLAS, University of Iowa, Iowa City, USABernd Fritzsch - Department of Biology, CLAS, University of Iowa, Iowa City, USA
- Resource Type
- Journal article
- Publication Details
- Ageing research reviews, Vol.59, pp.101042-101042
- DOI
- 10.1016/j.arr.2020.101042
- PMID
- 32173536
- NLM abbreviation
- Ageing Res Rev
- ISSN
- 1568-1637
- eISSN
- 1872-9649
- Publisher
- Elsevier B.V
- Grant note
- name: NIH/NIA, award: R01 AG060504, P01AG051443, R01 DC016099, R01 DC05135; name: National Instiute of Deafness and Communication Disorders, USA, award: R01 DC014093
- Language
- English
- Date published
- 05/2020
- Academic Unit
- Microbiology and Immunology; Anatomy and Cell Biology; Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center; Otolaryngology
- Record Identifier
- 9984070964302771
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