Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss.

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 deplet

SUBMITTER: Li J 

PROVIDER: S-EPMC11848329 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature