Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2024, Vol. 38 ›› Issue (5): 112-118.doi: 10.6040/j.issn.1673-3770.0.2023.448

• Review • Previous Articles    

Research progress on mTOR signaling pathway in cochlea

LI Yu, LIU Hao, WANG Min, FU Xiaolong, LI Wen   

  1. Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan 250117, Shandong, China
  • Published:2024-09-25

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Abstract: Deafness, a growing clinical challenge exacerbated by societal aging, increasingly affects patients' quality of life and adds to the social burden. Identifying effective intervention targets is crucial for the prevention and treatment of deafness. mTOR (target protein of rapamycin) is central to the processes of cell growth, metabolism, proliferation, and survival. Recent studies suggest that the mTOR pathway is essential for the proliferation, differentiation, maintenance, aging, and survival of cochlear inner ear hair cells and spiral neurons, which are essential for hearing. This paper reviews current research on the mTOR pathway in the cochlea, summarizes its regulatory mechanisms, and discusses unresolved issues and potential future research directions, highlighting the promise of mTOR as a novel therapeutic target for deafness.

CLC Number: 

  • R764.43
[1] Cortada M, Levano S, Bodmer D. mTOR signaling in the inner ear as potential target to treat hearing loss[J]. Int J Mol Sci, 2021, 22(12): 6368. doi:10.3390/ijms22126368
[2] Nadol JB Jr. Comparative anatomy of the cochlea and auditory nerve in mammals[J]. Hear Res, 1988,34(3):253-266. doi: 10.1016/0378-5955(88)90006-8
[3] ZHANG Wei, WANG Hongfang, XU Baohua. Overview of the main molecular mechanisms of biological aging[J]. Current Biotechnology, 2023, 13(2): 228-233. doi:10.19586/j.2095-2341.2022.0170
[4] Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease[J]. Cell, 2017, 168(6): 960-976. doi:10.1016/j.cell.2017.02.004
[5] WANG Zhen, YANG Luo, LIAO Min, et al. Research progress of mTOR pathway in pathogenesis of diabetic nephropathy[J]. Current Biotechnology, 2021, 11(3): 316-321. doi:10.19586/j.2095-2341.2020.0157
[6] Wei J J, Liu S W, Duan R X, et al. Research progress of mTOR in diabetic vascular disease [J]. Chinese Journal of Medical Molecular Biology,202,19(5):421-425.(in Chinese)doi:10.3870/j.issn.1672-8009.2022.05.012
[7] Murugan AK. mTOR: role in cancer, metastasis and drug resistance[J]. Semin Cancer Biol, 2019, 59: 92-111. doi:10.1016/j.semcancer.2019.07.003
[8] Tuo YL, Xiang M. mTOR: a double-edged sword for diabetes[J]. J Leukoc Biol, 2019, 106(2): 385-395. doi:10.1002/JLB.3MR0317-095RR
[9] Laplante M, Sabatini DM. mTOR signaling in growth control and disease[J]. Cell, 2012, 149(2): 274-293. doi:10.1016/j.cell.2012.03.017
[10] YAO Ruiyuan, WEI Hongyuan, LEI Jinye, et al. Progress on the role of mTOR signaling pathway in the pathogenesis and regulatory mechanisms[J]. Chinese Bulletin of Life Sciences, 2019, 31(2): 135-142. doi:10.13376/j.cbls/2019020
[11] SU Jie, YANG Fuyu, LI Meng, et al. GLP-1 protected the diabetic retinopathy through induction of autophagy in rats[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 30-34. doi:10.6040/j.issn.1673-3770.0.2021.125
[12] LANG Zhengrong, CHENG Gui, ZHANG Tao. Research progress on the relationship between cisplatin ototoxicity and autophagy[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2020, 34(2): 189-192. doi:10.13201/j.issn.1001-1781.2020.02.023
[13] Chen Y, Yu L. Autophagic lysosome reformation[J]. Exp Cell Res, 2013, 319(2): 142-146. doi:10.1016/j.yexcr.2012.09.004
[14] Li W, Li Y, Guan Y, et al. TNFAIP8L2/TIPE2 impairs autolysosome reformation via modulating the RAC1-MTORC1 axis[J]. Autophagy, 2021,17(6):1410-1425. doi: 10.1080/15548627.2020.1761748
[15] Suto T, Karonitsch T. The immunobiology of mTOR in autoimmunity[J]. J Autoimmun, 2020, 110: 102373. doi:10.1016/j.jaut.2019.102373
[16] Jiang H, Sha SH, Schacht J. Kanamycin alters cytoplasmic and nuclear phosphoinositide signaling in the organ of Corti in vivo[J]. J Neurochem, 2006, 99(1): 269-276. doi:10.1111/j.1471-4159.2006.04117.x
[17] Tisi A, Ramekers D, Flati V, et al. mTOR signaling in BDNF-treated guinea pigs after ototoxic deafening[J]. Biomedicines, 2022, 10(11): 2935. doi:10.3390/biomedicines10112935
[18] García-Mato á, Cervantes B, Rodríguez-de la Rosa L, et al. IGF-1 controls metabolic homeostasis and survival in HEI-OC1 auditory cells through AKT and mTOR signaling[J]. Antioxidants(Basel), 2023, 12(2): 233. doi:10.3390/antiox12020233
[19] Cortada M, Levano S, Hall MN, et al. mTORC2 regulates auditory hair cell structure and function[J]. iScience, 2023, 26(9): 107687. doi:10.1016/j.isci.2023.107687
[20] Kim HJ, Woo HM, Ryu J, et al. Conditional deletion of pten leads to defects in nerve innervation and neuronal survival in inner ear development[J]. PLoS One, 2013, 8(2): e55609. doi:10.1371/journal.pone.0055609
[21] Leitmeyer K, Glutz A, Radojevic V, et al. Inhibition of mTOR by rapamycin results in auditory hair cell damage and decreased spiral ganglion neuron outgrowth and neurite formation in vitro[J]. Biomed Res Int, 2015, 2015: 925890. doi:10.1155/2015/925890
[22] Shu YL, Li WY, Huang MQ, et al. Renewed proliferation in adult mouse cochlea and regeneration of hair cells[J]. Nat Commun, 2019, 10: 5530. doi:10.1038/s41467-019-13157-7
[23] Li XJ, Doetzlhofer A. LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling[J]. Proc Natl Acad Sci USA, 2020, 117(36): 22225-22236. doi:10.1073/pnas.2000417117
[24] Zhang Z, Gao S, Hu YN, et al. Ti3 C2 tx MXene composite 3D hydrogel potentiates mTOR signaling to promote the generation of functional hair cells in cochlea organoids[J]. Adv Sci(Weinh), 2022, 9(32): e2203557. doi:10.1002/advs.202203557
[25] Ye B, Wang Q, Hu H, et al. Restoring autophagic flux attenuates cochlear spiral ganglion neuron degeneration by promoting TFEB nuclear translocation via inhibiting MTOR[J]. Autophagy, 2019,15(6):998-1016.doi: 10.1080/15548627.2019.1569926
[26] Xiong W, Wei W, Qi Y, et al. Autophagy is required for remodeling in postnatal developing ribbon synapses of cochlear inner hair cells[J]. Neuroscience, 2020, 431: 1-16. doi:10.1016/j.neuroscience.2020.01.032
[27] Gao L, Kita T, Katsuno T, et al. Insulin-like growth factor 1 on the maintenance of ribbon synapses in mouse cochlear explant cultures[J]. Front Cell Neurosci, 2020, 14: 571155. doi:10.3389/fncel.2020.571155
[28] Varela-Nieto I, Murillo-Cuesta S, Calvino M, et al. Drug development for noise-induced hearing loss[J]. Expert Opin Drug Discov, 2020, 15(12): 1457-1471. doi:10.1080/17460441.2020.1806232
[29] YANG Kun, CHEN Lijuan, HE Xiaodan, et al. Comparative study of ototoxicity between kanamycin and 2-hydroxypropyl-β-cyclodextrin[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(4): 6-11. doi:10.6040/j.issn.1673-3770.0.2021.195
[30] HE Jingchun, RUAN Qingwei, HAN Miaomiao, et al. Establishment of sensorineural deafness model in C57 mice by cisplatin[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2014, 28(1): 1-5.doi: 10.6040/j.issn.1673-3770.0.2013.237
[31] Bodmer D, Levano-Huaman S. Sesn2/AMPK/mTOR signaling mediates balance between survival and apoptosis in sensory hair cells under stress[J]. Cell Death Dis, 2017, 8(10): e3068. doi:10.1038/cddis.2017.457
[32] Kim YC, Guan KL. mTOR: a pharmacologic target for autophagy regulation[J]. J Clin Invest, 2015, 125(1): 25-32. doi:10.1172/jci73939
[33] ZHOU Jiamin, SONG Yuwan, SUN Yan. Research progress of pyroptosis in senile degenerative diseases[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(4): 172-180. doi:10.6040/j.issn.1673-3770.0.2022.090
[34] GAO Xianting, LU Ling. Advances in the analysis and prevention of presbycusis[J]. International Journal of Otolaryngology-Head and Neck Surgery, 2018, 42(3): 174-178. doi:10.3760/cma.j.issn.1673-4106.2018.03.011
[35] Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice[J]. Nature, 2009, 460: 392-395. doi:10.1038/nature08221
[36] Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease[J]. Nature, 2013, 493: 338-345. doi:10.1038/nature11861
[37] Someya S, Yu W, Hallows WC, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction[J]. Cell, 2010, 143(5): 802-812. doi:10.1016/j.cell.2010.10.002
[38] Altschuler RA, Kabara L, Martin C, et al. Rapamycin added to diet in late mid-life delays age-related hearing loss in UMHET4 mice[J]. Front Cell Neurosci, 2021, 15: 658972. doi:10.3389/fncel.2021.658972
[39] Guo L, Cao W, Niu Y, et al. Autophagy regulates the survival of hair cells and spiral ganglion neurons in cases of noise, ototoxic drug, and age-induced sensorineural hearing loss[J]. Front Cell Neurosci, 2021, 15: 760422. doi:10.3389/fncel.2021.760422
[40] Fu X, Sun X, Zhang L, et al. Tuberous sclerosis complex-mediated mTORC1 overactivation promotes age-related hearing loss[J]. J Clin Invest, 2018, 128(11): 4938-4955. doi:10.1172/jci98058
[41] Zhang Y, Lv Z, Liu Y, et al. PIN1 protects hair cells and auditory HEI-OC1 cells against senescence by inhibiting the PI3K/akt/mTOR pathway[J]. Oxid Med Cell Longev, 2021, 2021: 9980444. doi:10.1155/2021/9980444
[42] Liu H, Li F, Li X, et al. Rapamycin ameliorates age-related hearing loss in C57BL/6J mice by enhancing autophagy in the SGNs[J]. Neurosci Lett, 2022, 772: 136493. doi:10.1016/j.neulet.2022.136493
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