{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:40:55Z","timestamp":1777887655171,"version":"3.51.4"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Sensorineural hearing loss (SNHL) is a major cause of disability worldwide, characterized by irreversible damage to cochlear hair cells and spiral ganglion neurons. Current treatments such as hearing aids and cochlear implants do not restore biological function. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key mechanism in acquired SNHL, including drug-, noise-, and age-related forms. This review systematically outlines the core molecular pathways of ferroptosis in SNHL, summarizes recent advances in ferroptosis-targeted interventions, and critically discusses current challenges and translational prospects. Although still largely preclinical, targeting ferroptosis represents a promising strategy for developing otoprotective therapies. Future research integrating novel technologies such as nano-delivery systems and single-cell omics may accelerate clinical translation.<\/jats:p>","DOI":"10.3389\/fneur.2026.1763297","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:20:08Z","timestamp":1777609208000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting ferroptosis in sensorineural hearing loss: mechanisms, therapeutics, and translational prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Lihong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyu","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]},{"name":"Department of Otorhinolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41434-020-0177-1","article-title":"Gene therapy development in hearing research in China","volume":"27","author":"Zhang","year":"2020","journal-title":"Gene Ther"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3390\/ijms27010102","article-title":"Cochlear homeostasis in sensorineural hearing loss: mechanisms, implications, and therapeutic prospects","volume":"27","author":"Vlajkovic","year":"2025","journal-title":"Int J Mol Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"ENEURO.0182","DOI":"10.1523\/ENEURO.0182-24.2024","article-title":"Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy","volume":"12","author":"Garrett","year":"2025","journal-title":"eNeuro"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1038\/s43587-025-00896-0","article-title":"Single-cell profiling identifies hair cell SLC35F1 deficiency as a signature of primate cochlear aging","volume":"5","author":"Sun","year":"2025","journal-title":"Nat Aging"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"11181","DOI":"10.1038\/s41467-025-66152-6","article-title":"Supporting cells orchestrate noise-induced hearing loss via a Gasdermin D-dependent signaling loop with hair cells","volume":"16","author":"Xiao","year":"2025","journal-title":"Nat Commun"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1607435","DOI":"10.3389\/fneur.2025.1607435","article-title":"A modern conceptual framework for study and treatment of Meniere's disease","volume":"16","author":"Chari","year":"2025","journal-title":"Front Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"18599","DOI":"10.1038\/srep18599","article-title":"Secreted factors from human vestibular schwannomas can cause Cochlear damage","volume":"5","author":"Dilwali","year":"2015","journal-title":"Sci Rep"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1007\/s12035-014-8951-y","article-title":"Spontaneous and partial repair of ribbon synapse in Cochlear inner hair cells after ototoxic withdrawal","volume":"52","author":"Liu","year":"2015","journal-title":"Mol Neurobiol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e39159","DOI":"10.7554\/eLife.39159","article-title":"Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss","volume":"8","author":"Celaya","year":"2019","journal-title":"eLife"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e13275","DOI":"10.1111\/acel.13275","article-title":"G6PD overexpression protects from oxidative stress and age-related hearing loss","volume":"19","author":"Berm\u00fadez-Mu\u00f1oz","year":"2020","journal-title":"Aging Cell"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1007\/s12264-025-01370-y","article-title":"Targeting programmed cell death in acquired sensorineural hearing loss: ferroptosis, necroptosis, and pyroptosis","volume":"41","author":"Zhang","year":"2025","journal-title":"Neurosci Bull"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1080\/14670100.2025.2516932","article-title":"The benefit of bilateral cochlear implants in adults with bilateral sensorineural hearing loss: a systematic review and meta-analysis","volume":"26","author":"Bance","year":"2025","journal-title":"Cochlear Implants Int"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1097\/AUD.0000000000000313","article-title":"Hearing instruments for unilateral severe-to-profound sensorineural hearing loss in adults: a systematic review and Meta-analysis","volume":"37","author":"Kitterick","year":"2016","journal-title":"Ear Hear"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/bjc.1972.33","article-title":"Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics","volume":"26","author":"Kerr","year":"1972","journal-title":"Br J Cancer"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e12915","DOI":"10.1111\/cpr.12915","article-title":"Programmed cell death pathways in hearing loss: a review of apoptosis, autophagy and programmed necrosis","volume":"53","author":"Wu","year":"2020","journal-title":"Cell Prolif"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"814891","DOI":"10.3389\/fncel.2021.814891","article-title":"Mechanism and prevention of spiral ganglion neuron degeneration in the cochlea","volume":"15","author":"Zhang","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: a regulated cell death Nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1021\/acscentsci.7b00589","article-title":"Resolving the role of lipoxygenases in the initiation and execution of ferroptosis","volume":"4","author":"Shah","year":"2018","journal-title":"ACS Cent Sci"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/s41419-019-2064-5","article-title":"ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation","volume":"10","author":"Park","year":"2019","journal-title":"Cell Death Dis"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2468853","DOI":"10.1080\/14756366.2025.2468853","article-title":"Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions","volume":"40","author":"Lv","year":"2025","journal-title":"J Enzyme Inhib Med Chem"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat Chem Biol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nat Chem Biol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1002\/jcsm.12953","article-title":"ACSL4 contributes to ferroptosis-mediated rhabdomyolysis in exertional heat stroke","volume":"13","author":"He","year":"2022","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.bbalip.2014.10.002","article-title":"Mammalian lipoxygenases and their biological relevance","volume":"1851","author":"Kuhn","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/s41589-020-0472-6","article-title":"Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis","volume":"16","author":"Zou","year":"2020","journal-title":"Nat Chem Biol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s10565-022-09778-2","article-title":"Ferroptosis: from regulation of lipid peroxidation to the treatment of diseases","volume":"39","author":"Lv","year":"2023","journal-title":"Cell Biol Toxicol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1038\/s41589-019-0408-1","article-title":"The chemical basis of ferroptosis","volume":"15","author":"Conrad","year":"2019","journal-title":"Nat Chem Biol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1016\/j.ymthe.2024.02.029","article-title":"Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL\/6 mice","volume":"32","author":"Liu","year":"2024","journal-title":"Mol Ther"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"122665","DOI":"10.1016\/j.biomaterials.2024.122665","article-title":"Application of self-assembly palladium single-atom nanozyme over polyoxometalates in protection against neomycin-induced hearing loss by inhibiting ferroptosis","volume":"311","author":"Huo","year":"2024","journal-title":"Biomaterials"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1430469","DOI":"10.3389\/fphar.2024.1430469","article-title":"Apoptosis, autophagy, ferroptosis, and pyroptosis in cisplatin-induced ototoxicity and protective agents","volume":"15","author":"Dai","year":"2024","journal-title":"Front Pharmacol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3390\/jox16010009","article-title":"Cisplatin as a xenobiotic agent: molecular mechanisms of actions and clinical applications in oncology","volume":"16","author":"Cecati","year":"2026","journal-title":"J Xenobiot"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"109487","DOI":"10.1016\/j.heares.2025.109487","article-title":"Bridging the gap: mechanisms and novel translational strategies to prevent cisplatin-induced ototoxicity","volume":"469","author":"Bai","year":"2025","journal-title":"Hear Res"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1039\/d5na00419e","article-title":"Dexamethasone-loaded lipid-polymeric nanoparticles to improve therapy for cisplatin-induced sensorineural hearing loss","volume":"8","author":"Qi","year":"2025","journal-title":"Nanoscale Adv"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e05663","DOI":"10.1002\/advs.202505663","article-title":"Cryopreserved human Otic neuronal spheroids self-assemble for functional connectivity analysis and long-term ototoxicity evaluation","volume":"13","author":"Sun","year":"2025","journal-title":"Adv Sci"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1111\/bph.70237","article-title":"Inositol hexaphosphate alleviates ototoxicity and age-related hearing loss by preserving cochlear hair cells in mice","volume":"183","author":"Tsai","year":"2025","journal-title":"Br J Pharmacol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.3390\/antiox13121578","article-title":"Cisplatin-induced hearing loss, oxidative stress, and antioxidants as a therapeutic strategy-a state-of-the-art review","volume":"13","author":"Rose","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"115550","DOI":"10.1016\/j.fct.2025.115550","article-title":"Paeoniflorin attenuates cisplatin induced ototoxicity by inhibiting ferroptosis mediated by HMGB1\/NRF2\/GPX4 pathway","volume":"202","author":"Chen","year":"2025","journal-title":"Food Chem Toxicol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"25720","DOI":"10.1021\/acs.jafc.4c07994","article-title":"Chiisanoside from the leaves of Acanthopanax sessiliflorus can resist cisplatin-induced ototoxicity by maintaining cytoskeletal homeostasis and inhibiting ferroptosis","volume":"72","author":"Teng","year":"2024","journal-title":"J Agric Food Chem"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.molcel.2015.06.011","article-title":"Glutaminolysis and transferrin regulate ferroptosis","volume":"59","author":"Gao","year":"2015","journal-title":"Mol Cell"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e2402671","DOI":"10.1002\/advs.202402671","article-title":"FOXO1-NCOA4 axis contributes to cisplatin-induced cochlea spiral ganglion neuron ferroptosis via ferritinophagy","volume":"11","author":"Wang","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.ymthe.2025.10.032","article-title":"Inhibiting ferroptosis in type I hair cells of the utricle might be a promising strategy for treating cisplatin-induced vestibulotoxicity","volume":"34","author":"Bi","year":"2025","journal-title":"Mol Ther"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"4413","DOI":"10.1016\/j.apsb.2024.05.024","article-title":"PGC-1\u03b1-mediated imbalance of mitochondria-lipid droplet homeostasis in neomycin-induced ototoxicity and nephrotoxicity","volume":"14","author":"Chen","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13578-024-01258-w","article-title":"Chemical screen in zebrafish lateral line identified compounds that ameliorate neomycin-induced ototoxicity by inhibiting ferroptosis pathway","volume":"14","author":"Fan","year":"2024","journal-title":"Cell Biosci"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/1782659","article-title":"Liproxstatin-1 protects hair cell-like HEI-OC1 cells and Cochlear hair cells against neomycin ototoxicity","volume":"2020","author":"Zheng","year":"2020","journal-title":"Oxidative Med Cell Longev"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"128","DOI":"10.2174\/157015910791233123","article-title":"Ischemia-reperfusion injury of the cochlea: pharmacological strategies for cochlear protection and implications of glutamate and reactive oxygen species","volume":"8","author":"Tabuchi","year":"2010","journal-title":"Curr Neuropharmacol"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"6166","DOI":"10.1007\/s12035-024-04675-7","article-title":"CD38 coordinates with NF-\u03baB to promote Cochlear inflammation in noise-induced hearing loss: the protective effect of apigenin","volume":"62","author":"Liu","year":"2025","journal-title":"Mol Neurobiol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.joto.2024.07.008","article-title":"Exploring the efficacy of (R)-PFI-2 hydrochloride in mitigating noise-induced hearing loss by targeting NLRP3 inflammasome and NF-\u03baB pathway to reduce inner ear inflammation","volume":"19","author":"Ren","year":"2024","journal-title":"J Otol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e38553","DOI":"10.1016\/j.heliyon.2024.e38553","article-title":"Ferroptosis, oxidative stress and hearing loss: mechanistic insights and therapeutic opportunities","volume":"10","author":"Yuan","year":"2024","journal-title":"Heliyon"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"4146","DOI":"10.3390\/ijms25084146","article-title":"Role of oxidative stress in sensorineural hearing loss","volume":"25","author":"Teraoka","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1309115","DOI":"10.3389\/fnagi.2024.1309115","article-title":"Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss","volume":"16","author":"Zeng","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2023.10.011","article-title":"Downregulation of KCNMA1 in mice accelerates auditory hair cells senescence via ferroptosis","volume":"134","author":"Tang","year":"2024","journal-title":"Neurobiol Aging"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s12031-023-02119-w","article-title":"Attenuation of age-related hearing impairment in senescence-accelerated mouse prone 8 (SAMP8) mice treated with fatty acid synthase inhibitor CMS121","volume":"73","author":"Pham","year":"2023","journal-title":"J Mol Neurosci"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e13909","DOI":"10.1111\/acel.13909","article-title":"Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice","volume":"22","author":"Okur","year":"2023","journal-title":"Aging Cell"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.neures.2025.02.008","article-title":"Metformin alleviates auditory cell senescence by mitophagy induction","volume":"213","author":"Cho","year":"2025","journal-title":"Neurosci Res"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s40246-023-00562-9","article-title":"LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL)","volume":"17","author":"Tisato","year":"2023","journal-title":"Hum Genomics"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"3373828","DOI":"10.1155\/2022\/3373828","article-title":"Treatment with the ferroptosis inhibitor ferrostatin-1 attenuates noise-induced hearing loss by suppressing ferroptosis and apoptosis","volume":"2022","author":"Ma","year":"2022","journal-title":"Oxidative Med Cell Longev"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"148445","DOI":"10.1016\/j.ijbiomac.2025.148445","article-title":"Intratympanic delivery of dexamethasone palmitate-loaded lipid nanoparticles in dual viscosity hyaluronic acids hydrogel for prolonged retention and hearing loss treatment","volume":"331","author":"Noh","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.3390\/cells14211658","article-title":"Study models for non-syndromic hearing loss","volume":"14","author":"Hoyau","year":"2025","journal-title":"Cells"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1408208","DOI":"10.3389\/fncel.2024.1408208","article-title":"Unraveling the molecular landscape of lead-induced cochlear synaptopathy: a quantitative proteomics analysis","volume":"18","author":"Bhatia","year":"2024","journal-title":"Front Cell Neurosci"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"153938","DOI":"10.1016\/j.tox.2024.153938","article-title":"Ferroptosis contributes to lead-induced cochlear spiral ganglion neurons injury","volume":"509","author":"Huang","year":"2024","journal-title":"Toxicology"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"109686","DOI":"10.1016\/j.envres.2020.109686","article-title":"Perfluoroalkyl substances exposure and hearing impairment in US adults","volume":"187","author":"Ding","year":"2020","journal-title":"Environ Res"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"5836","DOI":"10.3390\/ijerph17165836","article-title":"Serum per- and Polyfluoroalkyl substances are associated with increased hearing impairment: a re-analysis of the National Health and nutrition examination survey data","volume":"17","author":"Li","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-7244874\/v1","article-title":"PFAS exposure induces hearing loss by targeting Cochlear hair cells, ribbon synapses, and spiral ganglions [preprint]","author":"Bhatia","year":"2025","journal-title":"Res Sq"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.toxlet.2021.07.010","article-title":"Autophagy-dependent ferroptosis contributes to cisplatin-induced hearing loss","volume":"350","author":"Jian","year":"2021","journal-title":"Toxicol Lett"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"167024","DOI":"10.1016\/j.bbadis.2024.167024","article-title":"Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity","volume":"1870","author":"Lu","year":"2024","journal-title":"Biochim Biophys Acta Mol basis Dis"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41420-022-01025-1","article-title":"Ferroptosis is involved in PGPS-induced otitis media in C57BL\/6 mice","volume":"8","author":"Yan","year":"2022","journal-title":"Cell Death Discov"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"e18207","DOI":"10.1111\/jcmm.18207","article-title":"4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2\/HO-1 signalling pathway","volume":"28","author":"Zhang","year":"2024","journal-title":"J Cell Mol Med"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"632354","DOI":"10.3389\/fncel.2021.632354","article-title":"Inhibition of acyl-CoA synthetase long-chain family member 4 facilitates neurological recovery after stroke by regulation ferroptosis","volume":"15","author":"Chen","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"118363","DOI":"10.1016\/j.jep.2024.118363","article-title":"Ganoderic acid A mitigates dopaminergic neuron ferroptosis via inhibiting NCOA4-mediated ferritinophagy in Parkinson's disease mice","volume":"332","author":"Li","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"116790","DOI":"10.1016\/j.taap.2023.116790","article-title":"Luteolin inhibits the JAK\/STAT pathway to alleviate auditory cell apoptosis of acquired sensorineural hearing loss based on network pharmacology, molecular docking, molecular dynamics simulation, and experiments in vitro","volume":"482","author":"Guo","year":"2024","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.3389\/fphar.2019.01551","article-title":"Luteolin exerts neuroprotection via modulation of the p62\/Keap1\/Nrf2 pathway in intracerebral Hemorrhage","volume":"10","author":"Tan","year":"2020","journal-title":"Front Pharmacol"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"876","DOI":"10.3390\/cimb47110876","article-title":"Targeting ferroptosis in sensorineural hearing loss: a mechanistic review of therapeutic opportunities","volume":"47","author":"Liu","year":"2025","journal-title":"Curr Issues Mol Biol"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"114407","DOI":"10.1016\/j.eurpolymj.2025.114407","article-title":"Poly (2-isopropenyl-2-oxazoline) hydrogels as multipurpose drug delivery systems: tailoring molecular interactions for controlled loading and release","volume":"242","author":"Ghibu","year":"2025","journal-title":"Eur Polym J"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.3390\/polym16121708","article-title":"Poly(2-isopropenyl-2-oxazoline) as a versatile functional polymer for biomedical applications","volume":"16","author":"Kronek","year":"2024","journal-title":"Polymers"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"e2410120","DOI":"10.1002\/smll.202410120","article-title":"Conductive hydrogel systems enabling rapid and controllable release of guests at low-voltage region","volume":"21","author":"Shi","year":"2025","journal-title":"Small"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/s41420-025-02852-8","article-title":"Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho) lipid peroxidation as a potential therapeutic strategy","volume":"11","author":"Delehouz\u00e9","year":"2025","journal-title":"Cell Death Discov"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/s41420-025-02693-5","article-title":"Discovery of Zharp1-163 as a dual inhibitor of ferroptosis and necroptosis for the treatment of inflammatory disorders and kidney injury","volume":"11","author":"Ji","year":"2025","journal-title":"Cell Death Discov"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"3731","DOI":"10.1007\/s00210-024-03464-2","article-title":"Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation","volume":"398","author":"Shi","year":"2025","journal-title":"Naunyn Schmiedeberg's Arch Pharmacol"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.2174\/1389557522666220318111730","article-title":"Comparative review of effects of Pien Tze Huang and AnGong NiuHuang pill and their potential on treatment of central nervous system diseases","volume":"22","author":"Liu","year":"2022","journal-title":"Mini Rev Med Chem"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"117657","DOI":"10.1016\/j.jep.2023.117657","article-title":"Danlou tablet attenuates ischemic stroke injury and blood\u2013brain barrier damage by inhibiting ferroptosis","volume":"322","author":"Liu","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"121186","DOI":"10.1016\/j.jep.2026.121186","article-title":"Yangjing Zhongyu decoction ameliorates polycystic ovary syndrome via multi-organ ferroptosis inhibition: a mechanistic study","volume":"361","author":"Lu","year":"2026","journal-title":"J Ethnopharmacol"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"121001","DOI":"10.1016\/j.jep.2025.121001","article-title":"Chaihu Guizhi Ganjiang decoction attenuates chronic pancreatitis by suppressing acinar cell ferroptosis via regulating p53\/SLC7A11\/GPX4 pathway","volume":"358","author":"Li","year":"2026","journal-title":"J Ethnopharmacol"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3390\/ph19020251","article-title":"Yin-Dan-Ping-Gan capsule mitigates CCL4-induced liver fibrosis via regulating PPAR \u03b3\/GPX4 Signaling and suppressing ferroptosis","volume":"19","author":"Jiang","year":"2026","journal-title":"Pharmaceuticals"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"101451","DOI":"10.1016\/j.gendis.2024.101451","article-title":"Research progress on the use of traditional Chinese medicine to treat diseases by regulating ferroptosis","volume":"12","author":"Liu","year":"2024","journal-title":"Genes Dis"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"e01974","DOI":"10.1002\/advs.202501974","article-title":"Navigating transition metal-dependent cell death: mechanisms, crosstalk, and future directions","volume":"12","author":"Song","year":"2025","journal-title":"Adv Sci"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/ca.70057","article-title":"Programmed cell death and its therapeutic implications in Parkinson's disease: a review of apoptosis, autophagy, ferroptosis, and necroptosis","volume":"39","author":"Erekat","year":"2025","journal-title":"Clin Anat"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.molcel.2023.11.040","article-title":"The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death","volume":"84","author":"Ai","year":"2024","journal-title":"Mol Cell"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1038\/s12276-023-01069-y","article-title":"Regulated cell death pathways and their roles in homeostasis, infection, inflammation, and tumorigenesis","volume":"55","author":"Lee","year":"2023","journal-title":"Exp Mol Med"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1089\/ars.2022.0209","article-title":"Mitochondrial reactive oxygen species and lytic programmed cell death in acute inflammation","volume":"39","author":"Rius-P\u00e9rez","year":"2023","journal-title":"Antioxid Redox Signal"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1038\/s41418-024-01350-1","article-title":"Ferroptosis-based advanced therapies as treatment approaches for metabolic and cardiovascular diseases","volume":"31","author":"Maremonti","year":"2024","journal-title":"Cell Death Differ"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"1526519","DOI":"10.3389\/fnagi.2025.1526519","article-title":"Experimental validation and identification of ferroptosis-associated biomarkers for diagnostic and therapeutic targeting in hearing loss","volume":"17","author":"Yuan","year":"2025","journal-title":"Front Aging Neurosci"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"7999","DOI":"10.2147\/DDDT.S541415","article-title":"Pharmacokinetic and safety profiles of MIT-001, a novel ferroptosis inhibitor, after subcutaneous Administration in Healthy Participants","volume":"19","author":"Lee","year":"2025","journal-title":"Drug Des Devel Ther"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41392-022-00995-z","article-title":"LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB)","volume":"7","author":"Shi","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1186\/s12967-025-07103-z","article-title":"Mucoadhesive polydopamine-coated nanoparticle-mediated inner ear drug delivery for hearing loss treatment","volume":"23","author":"Kim","year":"2025","journal-title":"J Transl Med"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"122546","DOI":"10.1016\/j.carbpol.2024.122546","article-title":"Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection","volume":"345","author":"Jeong","year":"2024","journal-title":"Carbohydr Polym"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1186\/s12951-024-02686-z","article-title":"Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear","volume":"22","author":"Thakur","year":"2024","journal-title":"J Nanobiotechnol"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1594001","DOI":"10.3389\/fsurg.2025.1594001","article-title":"Porphyrin-based nanotechnology: a minimally invasive approach for drug delivery and cholesteatoma treatment","volume":"12","author":"Mahmoud","year":"2025","journal-title":"Front Surg"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"103165","DOI":"10.1016\/j.redox.2024.103165","article-title":"Modeling ferroptosis in human dopaminergic neurons: pitfalls and opportunities for neurodegeneration research","volume":"73","author":"Renner","year":"2024","journal-title":"Redox Biol"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"109021","DOI":"10.1016\/j.heares.2024.109021","article-title":"Murine cochlear damage models in the context of hair cell regeneration research","volume":"447","author":"Maraslioglu-Sperber","year":"2024","journal-title":"Hear Res"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"e0334351","DOI":"10.1371\/journal.pone.0334351","article-title":"Utility of cochlear perilymph biomarkers for hearing loss\u2014a systematic review","volume":"20","author":"Wanniarachchi","year":"2025","journal-title":"PLoS One"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41568-022-00459-0","article-title":"Targeting ferroptosis as a vulnerability in cancer","volume":"22","author":"Lei","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"eabl8920","DOI":"10.1126\/sciadv.abl8920","article-title":"Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor-induced dipeptidase-1 expression and glutathione depletion","volume":"8","author":"von M\u00e4ssenhausen","year":"2022","journal-title":"Sci Adv"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat Rev Mol Cell Biol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1763297\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:20:09Z","timestamp":1777609209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1763297\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":106,"alternative-id":["10.3389\/fneur.2026.1763297"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1763297","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"article-number":"1763297"}}