ArticleProceedings of the National Academy of Sciences of the United States of America2025
Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026Review
- Article
- Protective Effect of Selegiline (R-deprenyl) in Aminoglycoside-Induced Hearing Loss.Neurochemical research · 2025Article
- Aminoglycoside induces RIPOR2 translocation and phosphatidylserine externalization via distinct mechanisms.Frontiers in cellular neuroscience · 2025Article
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4 authors.
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Abstract
Aminoglycosides (AGs) are highly potent, broad-spectrum antibiotics frequently used as first-line treatments for multiple life-threatening infections. Despite their severe ototoxicity, causing irreversible hearing loss in millions of people annually, no preventive therapy has been approved. We previously reported that GABARAP and several other central autophagy proteins are essential for AG-induced hearing loss. This finding opens avenues for the rational design and development of inhibitors that selectively target proteins in this pathway, thereby mitigating AG ototoxicity. In this study, we generated a mouse model with a targeted deletion of GABARAPL1, a homolog of GABARAP, and another model deficient in both GABARAP and GABARAPL1. We found that normal hearing is unaffected by the depletion of these proteins. Remarkably, both proteins are essential for AG-induced hearing loss, with GABARAP playing a more significant role. To further explore the therapeutic potential, we designed and validated short hairpin RNAs targeting the mouse and human
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