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This review synthesizes current evidence on its involvement across a wide spectrum of auditory pathologies, including genetic syndromes such as CAPS and autosomal dominant deafness (DFNA) 34, as well as noise-induced, age-related, drug-induced, and viral hearing loss. Dysregulated activation of NLRP3 in the cochlea leads to the release of proinflammatory cytokines (IL-1B and IL-18) and pyroptotic cell death, contributing to irreversible cochlear damage.<\/jats:p>\n                  <jats:p>Experimental studies have demonstrated that pharmacological inhibition of NLRP3 via agents such as MCC950, oridonin and tranylcypromine can preserve auditory function. Gain-of-function mutations in the NLRP3 gene are frequently associated with both syndromic and nonsyndromic hearing loss, and animal models expressing these mutations replicate cochlear inflammation and hearing deficits, validating their pathogenic role. Clinically, IL-1B signaling blockers such as anakinra and canakinumab have shown efficacy in CAPS patients, stabilizing or improving hearing outcomes. Emerging selective NLRP3 inhibitors, including dapansutrilo and MCC950, are progressing through early-phase clinical trials. Additionally, natural compounds such as piceatannol and oridonin have demonstrated otoprotective effects in preclinical models of noise- and drug-induced hearing loss.<\/jats:p>\n                  <jats:p>Collectively, these findings position the NLRP3 inflammasome as a promising therapeutic target for SNHL. Future translational research should focus on validating NLRP3-targeting compounds in human trials, identifying biomarkers for early diagnosis, and exploring combination therapies that integrate anti-inflammatory, antioxidant, and regenerative strategies. Targeting NLRP3 may ultimately redefine treatment paradigms for preventing or halting progressive hearing loss.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s12974-025-03561-w","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T14:58:43Z","timestamp":1759589923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["NLRP3 inflammasome and hearing loss: from mechanisms to therapies"],"prefix":"10.1186","volume":"22","author":[{"given":"Silvia","family":"Murillo-Cuesta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Seoane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Cervantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Manuel","family":"Zubeldia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Varela-Nieto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,4]]},"reference":[{"key":"3561_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12979-023-00395-z","volume":"21","author":"R Liang","year":"2024","unstructured":"Liang R, Qi X, Cai Q, Niu L, Huang X, Zhang D, et al. 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