Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss

• DOI: 10.1073/pnas.2107357119
• Publication Date: 2022-03-02T16:42:38Z
• Authors: Xiaolong Fu; Peipei Li; Linqing Zhang; Yuning Song; Yachun An; Aizhen Zhang; Wenwen Liu; Chao Ye; Yuan Zhang; Rongyu Yue; Renjie Chai; Haibo Wang; Jiangang Gao
• Keywords: mTORC2; Ototoxicity; Sirolimus

The Food and Drug Administration–approved drug sirolimus, which inhibits mechanistic target of rapamycin (mTOR), is the leading candidate for targeting aging in rodents humans. We previously demonstrated that sirolimus could treat ARHL mice. In this study, we further demonstrate protects mice against cocaine-induced hearing loss. However, using efficacy safety tests, discovered developed substantial loss when administered high doses sirolimus. Using pharmacological genetic interventions murine models, inactivation mTORC2 major driver underlying Mechanistically, exerts its effects primarily through phosphorylating AKT/PKB signaling pathway, ablation P53 activity greatly attenuated severity phenotype mTORC2-deficient also found selective activation protect from acoustic trauma cisplatin-induced ototoxicity. Thus, discover a function suggest therapeutic represent potentially effective promising strategy to prevent sensorineural More importantly, elucidate side provide an evaluation criterion rational use clinical setting.