Abstract
Inflammasomes are multimeric protein complexes that can detect various physiological stimuli and danger signals. As a result, they perform a crucial function in the innate immune response. The NLRP3 inflammasome, as a vital constituent of the inflammasome family, is significant in defending against pathogen invasion and preserving cellhomeostasis. NLRP3 inflammasome dysregulation is connected to various pathological conditions, including inflammatory diseases, cancer, and cardiovascular and neurodegenerative diseases. This profile makes NLRP3 an applicable target for treating related diseases, and therefore, there are rising NLRP3 inhibitors disclosed for therapy. Herein, we summarized the updated advances in the structure, function, and inhibitors of NLRP3 inflammasome. Moreover, we aimed to provide an overview of the existing products and future directions for drug research and development.
[http://dx.doi.org/10.1016/S1097-2765(02)00599-3] [PMID: 12191486]
[http://dx.doi.org/10.1038/s41421-020-0167-x] [PMID: 32550001]
[http://dx.doi.org/10.3390/vaccines11020261] [PMID: 36851139]
[http://dx.doi.org/10.1083/jcb.201602089] [PMID: 27325789]
[http://dx.doi.org/10.1038/s41422-020-0295-8] [PMID: 32152420]
[http://dx.doi.org/10.1016/j.tibs.2022.10.002] [PMID: 36336552]
[http://dx.doi.org/10.1073/pnas.2121353119] [PMID: 35254907]
[http://dx.doi.org/10.1126/sciadv.abf4468]
[http://dx.doi.org/10.1016/j.jmb.2021.167309] [PMID: 34687713]
[http://dx.doi.org/10.1038/s41586-019-1295-z] [PMID: 31189953]
[http://dx.doi.org/10.1016/j.cell.2021.11.011] [PMID: 34861190]
[http://dx.doi.org/10.1016/j.tibs.2022.03.014] [PMID: 35382945]
[http://dx.doi.org/10.1038/s41586-022-04467-w] [PMID: 35114687]
[http://dx.doi.org/10.1038/s41586-022-05570-8] [PMID: 36442502]
[http://dx.doi.org/10.1038/s41577-019-0165-0] [PMID: 31036962]
[http://dx.doi.org/10.1073/pnas.1810524115] [PMID: 30279182]
[http://dx.doi.org/10.1016/j.drudis.2021.02.018] [PMID: 33636340]
[http://dx.doi.org/10.1146/annurev-immunol-081022-021207] [PMID: 36750315]
[http://dx.doi.org/10.1084/jem.20171848] [PMID: 29061692]
[http://dx.doi.org/10.1038/nrd.2018.97] [PMID: 30026524]
[http://dx.doi.org/10.1016/j.jare.2023.01.001] [PMID: 36610670]
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589]
[http://dx.doi.org/10.1038/s41423-021-00670-3] [PMID: 33850310]
[http://dx.doi.org/10.1016/j.molcel.2017.08.017] [PMID: 28943315]
[http://dx.doi.org/10.1038/s41418-022-00947-8] [PMID: 35110683]
[http://dx.doi.org/10.1016/j.lfs.2020.118918] [PMID: 33352170]
[http://dx.doi.org/10.1016/j.it.2018.01.009] [PMID: 29452983]
[http://dx.doi.org/10.1007/s10753-021-01439-6] [PMID: 34009550]
[http://dx.doi.org/10.1016/j.jaci.2021.04.018] [PMID: 34092352]
[http://dx.doi.org/10.3109/10409238.2012.694844] [PMID: 22681257]
[http://dx.doi.org/10.1016/j.coi.2012.12.004] [PMID: 23305783]
[http://dx.doi.org/10.1038/nature10558] [PMID: 22002608]
[http://dx.doi.org/10.1038/nature13683] [PMID: 25119034]
[http://dx.doi.org/10.1038/s41590-022-01192-4] [PMID: 35487985]
[http://dx.doi.org/10.1038/s41590-022-01188-0] [PMID: 35487984]
[http://dx.doi.org/10.1016/j.immuni.2016.01.012] [PMID: 27037191]
[http://dx.doi.org/10.1038/s41423-021-00740-6] [PMID: 34321623]
[http://dx.doi.org/10.1038/s41392-021-00650-z] [PMID: 34210954]
[http://dx.doi.org/10.3389/fimmu.2022.1007705] [PMID: 36275641]
[http://dx.doi.org/10.3389/fimmu.2017.00043] [PMID: 28191008]
[http://dx.doi.org/10.1146/annurev-immunol-032414-112227] [PMID: 25706096]
[http://dx.doi.org/10.1007/s10875-019-00638-z] [PMID: 31077002]
[http://dx.doi.org/10.1136/ard.2010.138420] [PMID: 21109514]
[http://dx.doi.org/10.1016/j.jaci.2022.08.019] [PMID: 36075321]
[http://dx.doi.org/10.1155/2019/7247238] [PMID: 31886308]
[http://dx.doi.org/10.1136/gut.2009.197822] [PMID: 20442201]
[PMID: 27993998]
[http://dx.doi.org/10.1016/j.bj.2023.01.004] [PMID: 36758943]
[http://dx.doi.org/10.1016/j.biopha.2021.111442] [PMID: 33667791]
[http://dx.doi.org/10.1016/j.immuni.2010.03.003] [PMID: 20303296]
[http://dx.doi.org/10.1016/j.cytogfr.2021.03.003] [PMID: 33773897]
[http://dx.doi.org/10.3389/fimmu.2019.00276] [PMID: 30873162]
[http://dx.doi.org/10.1016/j.pharmthera.2021.108053] [PMID: 34906598]
[http://dx.doi.org/10.1161/CIRCRESAHA.118.311362] [PMID: 29880500]
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.10.027] [PMID: 29126031]
[http://dx.doi.org/10.3390/biomedicines8070205] [PMID: 32664349]
[http://dx.doi.org/10.2147/JIR.S344730] [PMID: 34992411]
[http://dx.doi.org/10.1002/jcp.25930] [PMID: 28345767]
[http://dx.doi.org/10.1038/nature08938] [PMID: 20428172]
[http://dx.doi.org/10.3322/caac.21763] [PMID: 36633525]
[http://dx.doi.org/10.3322/caac.21208] [PMID: 24399786]
[http://dx.doi.org/10.1186/s12943-018-0900-3] [PMID: 30447690]
[http://dx.doi.org/10.1126/science.1156995] [PMID: 18403674]
[http://dx.doi.org/10.1080/10408444.2019.1692779] [PMID: 31905042]
[http://dx.doi.org/10.3892/or.2016.4569] [PMID: 26782741]
[http://dx.doi.org/10.1186/s12929-021-00724-8] [PMID: 33840390]
[http://dx.doi.org/10.1038/s41467-019-12370-8] [PMID: 31558756]
[http://dx.doi.org/10.1016/j.bbrc.2021.04.122] [PMID: 33975248]
[http://dx.doi.org/10.1038/srep36107] [PMID: 27786298]
[http://dx.doi.org/10.3390/cancers13102297] [PMID: 34064909]
[http://dx.doi.org/10.1126/stke.2772005pe14] [PMID: 15798102]
[http://dx.doi.org/10.1002/jcb.24389] [PMID: 22961880]
[http://dx.doi.org/10.4049/jimmunol.1400362] [PMID: 25172489]
[http://dx.doi.org/10.1038/sj.bjc.6603446] [PMID: 17088911]
[http://dx.doi.org/10.1002/jcp.25822] [PMID: 28121015]
[http://dx.doi.org/10.1038/onc.2017.381] [PMID: 29059152]
[http://dx.doi.org/10.1038/s41568-019-0123-y] [PMID: 30842595]
[http://dx.doi.org/10.3389/fimmu.2020.01444] [PMID: 32733479]
[http://dx.doi.org/10.4049/jimmunol.1002046] [PMID: 20855874]
[http://dx.doi.org/10.1038/s41590-021-00886-5] [PMID: 33707781]
[http://dx.doi.org/10.7326/AITC202105180] [PMID: 33971098]
[http://dx.doi.org/10.1016/j.biopsych.2008.11.029] [PMID: 19150053]
[http://dx.doi.org/10.1016/j.bbi.2012.12.008] [PMID: 23261775]
[http://dx.doi.org/10.1111/cns.12170] [PMID: 24279434]
[http://dx.doi.org/10.1007/s12035-015-9408-7] [PMID: 26362308]
[http://dx.doi.org/10.1016/j.bbi.2017.03.002] [PMID: 28263786]
[http://dx.doi.org/10.3389/fphar.2022.845185] [PMID: 35250595]
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930]
[http://dx.doi.org/10.1186/s13024-016-0088-1] [PMID: 26939933]
[http://dx.doi.org/10.3233/JAD-170634] [PMID: 28984607]
[http://dx.doi.org/10.1016/j.coi.2020.10.011] [PMID: 33181351]
[http://dx.doi.org/10.1016/j.arr.2020.101192] [PMID: 33059089]
[http://dx.doi.org/10.3390/biom9120850] [PMID: 31835423]
[http://dx.doi.org/10.1007/s00125-013-3023-9]
[http://dx.doi.org/10.3390/cells10020314] [PMID: 33546399]
[http://dx.doi.org/10.1083/jcb.200903124] [PMID: 19805629]
[http://dx.doi.org/10.1016/j.jid.2019.05.025] [PMID: 31252034]
[http://dx.doi.org/10.1097/FJC.0000000000000053] [PMID: 24336017]
[http://dx.doi.org/10.1097/FJC.0000000000000247] [PMID: 25915511]
[http://dx.doi.org/10.1021/acschemneuro.7b00124] [PMID: 28653829]
[http://dx.doi.org/10.1007/s12035-017-0467-9] [PMID: 28255908]
[http://dx.doi.org/10.1186/s12974-019-1471-y] [PMID: 30975164]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00733] [PMID: 29877709]
[http://dx.doi.org/10.1021/acs.jmedchem.9b01155] [PMID: 31626545]
[http://dx.doi.org/10.1016/j.ejmech.2022.114468] [PMID: 35635948]
[PMID: 11561079]
[http://dx.doi.org/10.1074/jbc.M211596200] [PMID: 12624100]
[http://dx.doi.org/10.1371/journal.pone.0029539] [PMID: 22216309]
[http://dx.doi.org/10.1038/s41589-019-0278-6] [PMID: 31086329]
[http://dx.doi.org/10.1038/s41589-019-0277-7] [PMID: 31086327]
[http://dx.doi.org/10.1124/pharmrev.120.000171] [PMID: 34117094]
[http://dx.doi.org/10.1021/acsmedchemlett.6b00198] [PMID: 27994733]
[http://dx.doi.org/10.1016/j.ejphar.2022.175091] [PMID: 35714692]
[http://dx.doi.org/10.1002/cmdc.201700270] [PMID: 28703484]
[http://dx.doi.org/10.1016/j.bmcl.2020.127571] [PMID: 32980515]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01250] [PMID: 36279149]
[http://dx.doi.org/10.1021/acsmedchemlett.9b00433] [PMID: 32292543]
[http://dx.doi.org/10.1016/j.bmcl.2020.127560] [PMID: 32956781]
[http://dx.doi.org/10.1021/acs.jmedchem.3c00175] [PMID: 36972104]
[http://dx.doi.org/10.1007/s00044-021-02740-7]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00149] [PMID: 35403430]
[http://dx.doi.org/10.1021/acsmedchemlett.2c00242] [PMID: 35978696]
[http://dx.doi.org/10.1172/JCI0216112] [PMID: 12464670]
[http://dx.doi.org/10.1084/jem.20171419] [PMID: 29021150]
[http://dx.doi.org/10.1016/j.bmcl.2020.127021] [PMID: 32057583]
[http://dx.doi.org/10.1016/j.bmcl.2022.128693] [PMID: 35314328]
[http://dx.doi.org/10.1016/j.bcp.2013.03.008] [PMID: 23506741]
[http://dx.doi.org/10.3390/molecules22020213] [PMID: 28146092]
[http://dx.doi.org/10.1016/j.bmcl.2021.128160] [PMID: 34062252]
[http://dx.doi.org/10.15252/emmm.201708689] [PMID: 29531021]
[http://dx.doi.org/10.3389/fcell.2020.00588] [PMID: 32754591]
[http://dx.doi.org/10.1016/j.bioorg.2019.103500] [PMID: 31869665]
[http://dx.doi.org/10.1021/acsptsci.1c00126] [PMID: 34423275]
[http://dx.doi.org/10.1016/j.jbc.2021.100597] [PMID: 33781745]
[http://dx.doi.org/10.1021/acs.jmedchem.0c01924] [PMID: 33332136]
[http://dx.doi.org/10.1016/j.chembiol.2017.08.011] [PMID: 28943355]
[http://dx.doi.org/10.1016/j.ejmech.2022.114194] [PMID: 35183871]
[http://dx.doi.org/10.1021/acs.joc.9b00138] [PMID: 30896160]
[http://dx.doi.org/10.1016/j.abb.2018.12.031] [PMID: 30641048]
[http://dx.doi.org/10.3390/molecules26133975] [PMID: 34209843]
[http://dx.doi.org/10.1021/acschemneuro.1c00831] [PMID: 35196855]
[http://dx.doi.org/10.1021/jm501072b] [PMID: 25418070]
[http://dx.doi.org/10.1002/cmdc.201600055] [PMID: 26990578]
[http://dx.doi.org/10.1021/acs.jmedchem.6b01624] [PMID: 28410442]
[http://dx.doi.org/10.1074/jbc.M109.082305] [PMID: 20093358]
[http://dx.doi.org/10.1016/j.bioorg.2022.106010] [PMID: 35914391]
[http://dx.doi.org/10.1073/pnas.1716095115] [PMID: 29378952]
[http://dx.doi.org/10.1111/all.15164] [PMID: 34716997]
[http://dx.doi.org/10.1186/s13075-018-1664-2] [PMID: 30075804]
[http://dx.doi.org/10.1073/pnas.2009680117] [PMID: 33257576]
[http://dx.doi.org/10.1074/jbc.M113.515080] [PMID: 24265316]
[http://dx.doi.org/10.1097/01.prs.0000479972.06934.83] [PMID: 26910701]
[http://dx.doi.org/10.1038/s41423-021-00683-y] [PMID: 33972740]
[http://dx.doi.org/10.1007/s40265-023-01838-z] [PMID: 36920652]
[http://dx.doi.org/10.1038/s41598-017-15314-8] [PMID: 29118366]
[http://dx.doi.org/10.1016/j.bmcl.2020.127399] [PMID: 32738997]
[http://dx.doi.org/10.1021/acs.jmedchem.1c01007] [PMID: 34506712]
[http://dx.doi.org/10.1016/j.ejmech.2022.114357] [PMID: 35428012]
[http://dx.doi.org/10.1016/j.bioorg.2023.106429] [PMID: 36841048]
[http://dx.doi.org/10.1021/acs.jmedchem.0c01743] [PMID: 33440945]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01967] [PMID: 36786612]
[http://dx.doi.org/10.1038/s41467-018-04947-6] [PMID: 29959312]
[http://dx.doi.org/10.1016/j.ejmech.2022.114919] [PMID: 36399877]
[http://dx.doi.org/10.1016/j.ejmcr.2022.100100] [PMID: 37033416]
[http://dx.doi.org/10.1016/j.bcp.2018.07.039] [PMID: 30071202]
[http://dx.doi.org/10.3390/molecules25245960] [PMID: 33339319]
[http://dx.doi.org/10.1016/j.bioorg.2020.103748] [PMID: 32179281]
[http://dx.doi.org/10.1016/j.ejmech.2021.113417] [PMID: 33845232]
[http://dx.doi.org/10.1021/acs.jnatprod.0c00478] [PMID: 32989985]
[http://dx.doi.org/10.1021/acsmedchemlett.1c00597] [PMID: 35450356]
[http://dx.doi.org/10.15252/embr.202153499] [PMID: 34882936]
[http://dx.doi.org/10.1016/j.molimm.2018.09.004] [PMID: 30396035]
[http://dx.doi.org/10.3389/fimmu.2021.739953] [PMID: 34745110]
[http://dx.doi.org/10.1038/s41401-023-01054-1] [PMID: 36964308]
[http://dx.doi.org/10.1016/j.apsb.2022.09.014] [PMID: 36873170]
[PMID: 36627344]
[http://dx.doi.org/10.1111/bph.16036] [PMID: 36668704]
[http://dx.doi.org/10.1021/acs.orglett.6b03435] [PMID: 27978645]
[http://dx.doi.org/10.1016/j.jbc.2022.102696] [PMID: 36379253]
[http://dx.doi.org/10.1002/ctm2.496] [PMID: 34323410]
[http://dx.doi.org/10.1016/j.bbi.2020.09.017] [PMID: 32971182]
[http://dx.doi.org/10.1021/acs.jnatprod.0c00200] [PMID: 32584575]
[http://dx.doi.org/10.1021/acs.jnatprod.2c00568] [PMID: 36286259]
[http://dx.doi.org/10.1021/acs.jnatprod.0c00288] [PMID: 32628479]
[http://dx.doi.org/10.1016/j.bioorg.2023.106362] [PMID: 36657273]
[http://dx.doi.org/10.1016/j.bcp.2021.114645] [PMID: 34090877]
[http://dx.doi.org/10.1016/j.intimp.2023.109819] [PMID: 36738671]
[http://dx.doi.org/10.3389/fphar.2021.818326] [PMID: 35095532]