# NLRP3 Inflammasome Role and NLRP3 Inhibitors in Sensorineural Hearing Loss **Authors:** Mireia Toledano-Pinedo, José Marco-Contelles, Alexey V. Dobrydnev PMC · DOI: 10.3390/biom16020186 · Biomolecules · 2026-01-26 ## TL;DR This paper reviews the role of the NLRP3 inflammasome in hearing loss and explores promising inhibitors for its treatment. ## Contribution The paper highlights recent experimental findings and identifies promising NLRP3 inhibitors with good pharmacological profiles. ## Key findings - The NLRP3 inflammasome contributes to sensorineural hearing loss through inflammatory pathways. - Recent studies show that NLRP3 inhibitors have effective pharmacological and pharmacokinetic properties. - Promising small molecule inhibitors could lead to new clinical therapies for hearing loss. ## Abstract Herein, we will review the function of the NLRP3 inflammasome in hearing loss (HL), summarize the most significant experimental results described in recent years, describe the biological mechanisms involved in the role of NLRP3 inflammasome in HL, and highlight some of the most promising small NLRP3 inhibitors for its clinical therapy, showing excellent pharmacological effects and good pharmacodynamic/pharmacokinetic profiles. ## Linked entities - **Genes:** NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] - **Diseases:** hearing loss (MONDO:0005365) ## Full-text entities - **Genes:** Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, Musk (muscle, skeletal, receptor tyrosine kinase) [NCBI Gene 18198] {aka Mdk4, Mlk, Nsk1, Nsk2, Nsk3}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Aicda (activation-induced cytidine deaminase) [NCBI Gene 11628] {aka Aid, Arp2}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, Gfi1 (growth factor independent 1 transcription repressor) [NCBI Gene 14581] {aka Gfi-1, Pal-1, Pal1}, Pou4f3 (POU domain, class 4, transcription factor 3) [NCBI Gene 18998] {aka Brn3.1, Brn3c, ddl, dreidel}, Sgk1 (serum/glucocorticoid regulated kinase 1) [NCBI Gene 20393] {aka Sgk}, Cadps (Ca2+-dependent secretion activator) [NCBI Gene 27062] {aka CAPS, CAPS1, mKIAA1121}, AICDA (activation induced cytidine deaminase) [NCBI Gene 57379] {aka AID, ARP2, CDA2, HEL-S-284, HIGM2}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Slc26a4 (solute carrier family 26, member 4) [NCBI Gene 23985] {aka Pds, pendrin}, Il1r2 (interleukin 1 receptor, type II) [NCBI Gene 16178] {aka CD121b, Il1r-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Cx3cr1 (C-X3-C motif chemokine receptor 1) [NCBI Gene 13051] {aka mCX3CR1}, IL18 (interleukin 18) [NCBI Gene 397057] {aka IL-18}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 100514823], CASP1 (caspase 1, apoptosis-related cysteine peptidase) [NCBI Gene 397319], Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, IL1B (interleukin 1 beta) [NCBI Gene 397122] {aka IL1B1}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, Gsdmd (gasdermin D) [NCBI Gene 69146] {aka 1810036L03Rik, DF5L, Dfna5l, GsdmD-1, Gsdmdc1, M2-4}, TXNIP (thioredoxin interacting protein) [NCBI Gene 10628] {aka ARRDC6, EST01027, HHCPA78, THIF, VDUP1}, Sts (steroid sulfatase) [NCBI Gene 20905] {aka ArsC}, Nek7 (NIMA (never in mitosis gene a)-related expressed kinase 7) [NCBI Gene 59125] {aka 2810460C19Rik}, TNFRSF1B (TNF receptor superfamily member 1B) [NCBI Gene 7133] {aka CD120b, TBPII, TNF-R-II, TNF-R75, TNFBR, TNFR1B}, SAA [NCBI Gene 6287], MEFV (MEFV innate immunity regulator, pyrin) [NCBI Gene 4210] {aka FMF, MEF, PAAND, TRIM20} - **Diseases:** Cryopyrin-associated periodic syndromes (MESH:D056587), infection (MESH:D007239), neurotoxicity (MESH:D020258), deafness (MESH:D003638), Alzheimer's disease (MESH:D000544), renal failure (MESH:D051437), behavioral abnormalities (MESH:D001523), tinnitus (MESH:D014012), intracranial tumors (MESH:D009369), sensory disorder (MESH:D012678), cochlear injury (MESH:D015834), toxicity (MESH:D064420), arthralgia (MESH:D018771), auditory dysfunction (MESH:D006311), FCAS (MESH:C538437), endolymphatic hydrops (MESH:D018159), neurological complications (MESH:D002493), ARHL (MESH:D010024), Pericarditis (MESH:D010493), auto-inflammation (MESH:D007249), neurodegenerative disorders (MESH:D019636), injury to (MESH:D014947), audiovestibular abnormalities (MESH:D000014), rheumatoid arthritis (MESH:D001172), SGN (MESH:D050723), mitochondrial dysfunction (MESH:D028361), MD (MESH:D008575), SNHL (MESH:D006319), genetic disorders (MESH:D030342), HL diseases (MESH:D034381), associated autoinflammatory disease (MESH:D056660), necrosis (MESH:D009336), VS (MESH:D009464), fever (MESH:D005334), NIHL (MESH:D006317), Nonsyndromic HL (MESH:C580334), Musculoskeletal impairment (MESH:D009140), inner ear injury (MESH:D007759), presbycusis (MESH:D011304), amyloidosis (MESH:D000686), SGN degeneration (MESH:D009410), urticarial (MESH:C535817), rash (MESH:D005076), urticaria (MESH:D014581), neonatal hyperbilirubinemia (MESH:D051556), MWS (OMIM:191900), CMV (MESH:D003586), Auto-Inflammatory Disorders (MESH:D018467), fatigue (MESH:D005221), systemic (MESH:D015619) - **Chemicals:** bilirubin (MESH:D001663), Ori (MESH:C011959), monosodium urate (MESH:D014527), DFNA34 (-), Cisplatin (MESH:D002945), Canakinumab (MESH:C541220), URMC-099 (MESH:C583037), aminoglycoside (MESH:D000617), tocilizumab (MESH:C502936), hematoxylin (MESH:D006416), BAY11-7082 (MESH:C434003), eosin (MESH:D004801), glutamate (MESH:D018698), PCT (MESH:C041525), KM (MESH:D007612), ROS (MESH:D017382), MCC950 (MESH:C000597426), LPS (MESH:D008070) - **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Adeno-associated virus (species) [taxon 272636], Sus scrofa (pig, species) [taxon 9823] - **Mutations:** p.Ser624Arg, D301N, A439V, E313K, p.I288M, c.1872C>G, T348M, V198M, p.Tyr861Cys, p.R761H - **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), MCC950 — Homo sapiens (Human), Scleromyxedema, Finite cell line (CVCL_IL06), HEI-OC-1 — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_D899) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12938068/full.md ## Figures 6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938068/full.md ## References 36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938068/full.md --- Source: https://tomesphere.com/paper/PMC12938068