ArticleProceedings of the National Academy of Sciences of the United States of America2022
Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Differential regulation of monocyte exhaustion by distinct TLR agonists and underlying mechanisms.Cell communication and signaling : CCS · 2026Article
- Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026Review
- The mTOR Pathway in Hearing Disorders: Mechanistic Links to Aging, Regeneration, and Neurodegeneration.Molecular neurobiology · 2026Review
- Conventional and Shared Genetic Association Analysis Between Diabetes Mellitus and Sensorineural Hearing Loss.Human mutation · 2026Article
- Presbycusis: Pathology, Signal Pathways, and Therapeutic Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- FGF13 prevents age-related hearing loss by protecting spiral ganglion neurons and ribbon synapses from injury.Cell death discovery · 2025Article
- TNFAIP8L2 maintains hair cell function and regulates age-related hearing loss via mTORC1 signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Kolliker's Organ and Its Functional Role in the Development of Corti's Organ and Auditory Systems.Audiology research · 2025Review
- Transforming Growth Factor-β-Activated Protein 1 (TAK1) Regulates Necroptosis in Age-Related Hearing Loss.Aging cell · 2025Article
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Development of the inner ear and regeneration of hair cells after hearing impairment.Fundamental research · 2025Review
- Pathophysiological insights and therapeutic developments in age-related hearing loss: a narrative review.Frontiers in aging neuroscience · 2025Review
- Pharmacological Approaches to Hearing Loss.Pharmacological reviews · 2024Review
- The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes.The journal of international advanced otology · 2024Article
- Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation.Neuroscience bulletin · 2024Review
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) protects hair cells from cisplatin-induced ototoxicity in vitro: possible relation to the activities of p38 MAPK signaling pathway.Archives of toxicology · 2023Article
- mTORC2 regulates auditory hair cell structure and function.iScience · 2023Article
- TIGAR Protects Cochlear Hair Cells against Teicoplanin-Induced Damage.Molecular neurobiology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Food and Drug Administration–approved drug sirolimus, which inhibits mechanistic target of rapamycin (mTOR), is the leading candidate for targeting aging in rodents and humans. We previously demonstrated that sirolimus could treat ARHL in mice. In this study, we further demonstrate that sirolimus protects mice against cocaine-induced hearing loss. However, using efficacy and safety tests, we discovered that mice developed substantial hearing loss when administered high doses of sirolimus. Using pharmacological and genetic interventions in murine models, we demonstrate that the inactivation of mTORC2 is the major driver underlying hearing loss. Mechanistically, mTORC2 exerts its effects primarily through phosphorylating in the AKT/PKB signaling pathway, and ablation of P53 activity greatly attenuated the severity of the hearing phenotype in mTORC2-deficient mice. We also found that the selective activation of mTORC2 could protect mice from acoustic trauma and cisplatin-induced ototoxicity. Thus, in this study, we discover a function of mTORC2 and suggest that its therapeutic activation could represent a potentially effective and promising strategy to prevent sensorineural hearing loss. More importantly, we elucidate the side effects of sirolimus and provide an evaluation criterion for the rational use of this drug in a clinical setting.
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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.