ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
A novel role of cytosolic protein synthesis inhibition in aminoglycoside ototoxicity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus.The Journal of antimicrobial chemotherapy · 2026Article
- Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.Cell death discovery · 2024Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.bioRxiv : the preprint server for biology · 2024Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.Frontiers in neurology · 2024Article
- Insights into the molecular underlying mechanisms and therapeutic potential of endoplasmic reticulum stress in sensorineural hearing loss.Frontiers in molecular neuroscience · 2024Review
- Otoprotection against aminoglycoside- and cisplatin-induced ototoxicity focusing on the upstream drug uptake pathway.Journal of the Chinese Medical Association : JCMA · 2024Review
- Contemporary Progress and Opportunities in RNA-Targeted Drug Discovery.ACS medicinal chemistry letters · 2023Review
- Otoprotective Effects of Fucoidan Reduce Cisplatin-Induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells.International journal of molecular sciences · 2023Article
- RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss.Developmental cell · 2022Article
- ASK1 is a novel molecular target for preventing aminoglycoside-induced hair cell death.Journal of molecular medicine (Berlin, Germany) · 2022Article
- mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss.International journal of molecular sciences · 2021Review
- Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
- The relationship between the structure and toxicity of aminoglycoside antibiotics.Bioorganic & medicinal chemistry letters · 2020Review
- Exosomes mediate sensory hair cell protection in the inner ear.The Journal of clinical investigation · 2020Article
- CRISPR/Cas9: targeted genome editing for the treatment of hereditary hearing loss.Journal of applied genetics · 2020Review
- Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia.Journal of clinical medicine · 2020Review
- Use of a fluorescence assay to determine relative affinities of semisynthetic aminoglycosides to small RNAs representing bacterial and mitochondrial A sites.Bioorganic & medicinal chemistry · 2019Article
- Drug-induced Stress Granule Formation Protects Sensory Hair Cells in Mouse Cochlear Explants During Ototoxicity.Scientific reports · 2019Article
- Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Ototoxicity is a main dose-limiting factor in the clinical application of aminoglycoside antibiotics. Despite longstanding research efforts, our understanding of the mechanisms underlying aminoglycoside ototoxicity remains limited. Here we report the discovery of a novel stress pathway that contributes to aminoglycoside-induced hair cell degeneration. Modifying the previously developed bioorthogonal noncanonical amino acid tagging method, we used click chemistry to study the role of protein synthesis activity in aminoglycoside-induced hair cell stress. We demonstrate that aminoglycosides inhibit protein synthesis in hair cells and activate a signaling pathway similar to ribotoxic stress response, contributing to hair cell degeneration. The ability of a particular aminoglycoside to inhibit protein synthesis and to activate the c-Jun N-terminal kinase (JNK) pathway correlated well with its ototoxic potential. Finally, we report that a Food and Drug Administration-approved drug known to inhibit ribotoxic stress response also prevents JNK activation and improves hair cell survival, opening up novel strategies to prevent and treat aminoglycoside ototoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.