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A phosphatase and protease library screen to elucidate aminoglycoside-mediated murine sensorineural hair cell damage processes

Abstract

Ototoxicity has implications on hearing loss and vestibular system function due to its damaging effects on the sensorineural cells of the inner ear. These cells have variable sensitivity to ototoxic compounds and limited ability to regenerate making hearing loss due to their death permanent. It is vital to find neuroprotective compounds to develop as drug candidates to prevent damage to these cells, thus prevent hearing loss. An in vitro library screening-assay of protease and phosphatase inhibitors activating a number of signaling pathways and downstream effectors contributing to hair cell survival producing possible new drug candidates for future testing in developing treatment techniques. The 6 compounds with effective dose-dependent results from this experiment can help clarify the processes and possible new target areas for the treatment of sensorineural hearing loss in mammals with further research.

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