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O'Sullivan ME, Perez A, Lin R, et al. Towards the Prevention of Aminoglycoside-Related Hearing Loss. Front Cell Neurosci. 2017;11:325doi: 10.3389/fncel.2017.00325.
O'Sullivan, M. E., Perez, A., Lin, R., Sajjadi, A., Ricci, A. J., & Cheng, A. G. (2017). Towards the Prevention of Aminoglycoside-Related Hearing Loss. Frontiers in cellular neuroscience, 11325. https://doi.org/10.3389/fncel.2017.00325
O'Sullivan, Mary E, et al. "Towards the Prevention of Aminoglycoside-Related Hearing Loss." Frontiers in cellular neuroscience vol. 11 (2017): 325. doi: https://doi.org/10.3389/fncel.2017.00325
O'Sullivan ME, Perez A, Lin R, Sajjadi A, Ricci AJ, Cheng AG. Towards the Prevention of Aminoglycoside-Related Hearing Loss. Front Cell Neurosci. 2017 Oct 18;11:325. doi: 10.3389/fncel.2017.00325. eCollection 2017. PMID: 29093664; PMCID: PMC5651232.
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Front Cell Neurosci. 2017 Oct 18;11:325. doi: 10.3389/fncel.2017.00325. eCollection 2017.

Towards the Prevention of Aminoglycoside-Related Hearing Loss.

Frontiers in cellular neuroscience

Mary E O'Sullivan, Adela Perez, Randy Lin, Autefeh Sajjadi, Anthony J Ricci, Alan G Cheng

Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.
  2. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, United States.

PMID: 29093664 PMCID: PMC5651232 DOI: 10.3389/fncel.2017.00325

Abstract

Aminoglycosides are potent antibiotics deployed worldwide despite their known side-effect of sensorineural hearing loss. The main etiology of this sensory deficit is death of inner ear sensory hair cells selectively triggered by aminoglycosides. For decades, research has sought to unravel the molecular events mediating sensory cell demise, emphasizing the roles of reactive oxygen species and their potentials as therapeutic targets. Studies in recent years have revealed candidate transport pathways including the mechanotransducer channel for drug entry into sensory cells. Once inside sensory cells, intracellular targets of aminoglycosides, such as the mitochondrial ribosomes, are beginning to be elucidated. Based on these results, less ototoxic aminoglycoside analogs are being generated and may serve as alternate antimicrobial agents. In this article, we review the latest findings on mechanisms of aminoglycoside entry into hair cells, their intracellular actions and potential therapeutic targets for preventing aminoglycoside ototoxicity.

Keywords: aminoglycoside antibiotics; mRNA misreading; mechanotransducer channel; ototoxicity; ribosome

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