{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:42:29Z","timestamp":1792384949674,"version":"4.4.0"},"reference-count":97,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Hearing loss (HL) is one of the most common sensory impairments worldwide and has substantial effects on quality of life and daily functioning. Although cochlear implants and hearing aids have markedly improved the management of hearing impairment, these devices do not directly address the underlying pathogenic mechanisms of HL. This review aims to summarize the pathophysiology and classification of HL and to discuss the potential therapeutic applications of small molecules (SMs) in its management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review focuses on the major pathological mechanisms involved in different forms of HL and summarizes preclinical and clinically relevant SM\u2010based therapeutic approaches. The reviewed strategies include pharmacological chaperones, transcriptional modulation, ion\u2010channel modulators, neuroprotective compounds, apoptosis inhibitors, and regenerative approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SMs possess physicochemical properties that make them suitable for targeting specific molecular pathways involved in HL. Current evidence suggests that SM\u2010based interventions may act through diverse mechanisms, including attenuation of oxidative stress, inflammation, and apoptosis; modulation of ion channels; support of auditory neuron survival and function; and promotion of regenerative signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SM\u2010based therapeutic approaches represent promising strategies for addressing the molecular and cellular mechanisms underlying HL. These approaches may provide valuable directions for future research and support the development of targeted therapies for individuals with hearing impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.73323","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:14:37Z","timestamp":1791634477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Small Molecule Therapeutic Approaches With a Greater Focus on Hearing Loss: A Review"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-7474","authenticated-orcid":false,"given":"Maryam","family":"Naghinejad","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7228-8826","authenticated-orcid":false,"given":"Farzaneh","family":"Motallebi","sequence":"additional","affiliation":[{"name":"Student Research Committee Golestan University of Medical Sciences Gorgan Iran"},{"name":"Department of Medical Genetics, Faculty of Advanced Technologies in Medicine Golestan University of Medical Science Gorgan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7457-0194","authenticated-orcid":false,"given":"Elaheh","family":"Hasani","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran"},{"name":"Student Research Committee Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8475-0905","authenticated-orcid":false,"given":"Moein","family":"Kohkalani","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran"},{"name":"Student Research Committee Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1865-5040","authenticated-orcid":false,"given":"Sepideh","family":"Parvizpour","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Advanced Medical Sciences Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3398-941X","authenticated-orcid":false,"given":"Sima","family":"Mansoori Derakhshan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.05.003"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.02.001"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1177791"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1269577"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2022.02.015"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909494"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112168"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1502309"},{"key":"e_1_2_14_10_1","first-page":"1","article-title":"Hearing Loss Drug Discovery and Medicinal Chemistry: Current Status, Challenges, and Opportunities","volume":"61","author":"Cousins R.","year":"2022","journal-title":"Progress in Medicinal Chemistry"},{"key":"e_1_2_14_11_1","first-page":"111","article-title":"Sensorineural Hearing Loss (SNHL)","volume":"1","author":"Larem A.","year":"2021","journal-title":"Textbook of Clinical Otolaryngology"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/978-2-88945-000-8"},{"key":"e_1_2_14_13_1","first-page":"479","volume-title":"Handbook of Clinical Neurology","author":"Hopkins K.","year":"2015"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25105391"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2023.108783"},{"issue":"2","key":"e_1_2_14_16_1","first-page":"98","article-title":"Hearing Loss in Adults: Differential Diagnosis and Treatment","volume":"100","author":"Michels T. 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