含pyrin结构域NOD样受体家族3(NLRP3)炎性体抑制剂及其作用机制研究进展
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摘要
含pyrin结构域NOD样受体家族3(NLRP3)炎性体是由NLRP3、凋亡相关斑点样蛋白(ASC)及胱天蛋白酶1(caspase-1)组成的蛋白复合体,主要介导白细胞介素1β(IL-1β)和IL-18的前体成熟参与炎症反应。NLRP3炎性体的异常活化与代谢紊乱、神经退行性疾病、自身免疫性疾病等炎症性疾病的发生发展关系密切。寻找并开发NLRP3炎性体的有效抑制剂成为治疗炎症性疾病的新策略。我们总结了已报道的在NLRP3炎性体活化的起始阶段和激活阶段发挥作用的抑制剂及其作用机制,期望为开发以NLRP3炎性体为靶点的抗炎药物提供新思路。
引文
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[34] Pal A,Neo K,Rajamani L,et al.Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides[J/OL].Sci Rep,2019,9(1):4913.DOI:10.1038/s41598-019-41211-3.
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[3] Swanson K V,Deng M,Ting J P Y.The NLRP3 inflammasome:molecular activation and regulation to therapeutics[J].Nat Rev Immunol,2019 Apr 29.DOI:10.1038/s41577-019-0165-0.[Epub ahead of print].
[4] Groslambert M,Py B F.Spotlight on the NLRP3 inflammasome pathway[J].J Inflamm Res,2018,11:359-374.
[5] Zou J,Yang Y,Yang Y,et al.Polydatin suppresses proliferation and metastasis of non-small cell lung cancer cells by inhibiting NLRP3 inflammasome activation via NF-κB pathway[J].Biomed Pharmacother,2018,108:130-136.
[6] Song D,Zhao J,Deng W,et al.Tannic acid inhibits NLRP3 inflammasome-mediated IL-1β production via blocking NF-κB signaling in macrophages[J].Biochem Biophys Res Commun,2018,503(4):3078-3085.
[7] Zhao X,Pu D,Zhao Z,et al.Teuvincenone F suppresses LPS-induced inflammation and NLRP3 inflammasome activation by attenuating NEMO ubiquitination[J/OL].Front Pharmacol,2017,8:565.DOI:10.3389/fphar.2017.00565.
[8] Cummins C B,Wang X,Sommerhalder C,et al.Natural compound oridonin inhibits endotoxin-induced inflammatory response of activated hepatic stellate cells[J/OL].Biomed Res Int,2018,2018:6137420.DOI:10.1155/2018/6137420.
[9] He H,Jiang H,Chen Y,et al.Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity[J].Nat Commun,2018,9:2550.DOI:10.1038/s41467-018-04947-6.
[10] Shi H,Wang Y,Li X,et al.NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7,a new inflammasome component[J].Nat Immunol,2016,17(3):250-258.
[11] Mathur A,Hayward J A,Man S M.Molecular mechanisms of inflammasome signaling[J].J Leukoc Biol,2018,103(2):233-257.
[12] Jiang H,He H,Chen Y,et al.Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders[J].J Exp Med,2017,214(11):3219-3238.
[13] MacDonald J A,Wijekoon C P,Liao K C,et al.Biochemical and structural aspects of the ATP-binding domain in inflammasome-forming human NLRP proteins[J].IUBMB Life,2013,65(10):851-862.
[14] Sandall C F,MacDonald J A.Effects of phosphorylation on the NLRP3 inflammasome[J].Arch Biochem Biophys,2019 Mar 5.pii:S0003-9861(18)31012-9.DOI:10.1016/j.abb.2019.02.020.[Epub ahead of print].
[15] Juliana C,Fernandes-Alnemri T,Wu J,et al.Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome[J].J Biol Chem,2010,285(13):9792-9802.
[16] He Y,Varadarajan S,Muňoz-Planillo R,et al.3,4-methylenedioxy-β-nitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome[J].J Biol Chem,2014,289(2):1142-1150.
[17] Marchetti C,Swartzwelter B,Gamboni F,et al.OLT1177,a β-sulfonyl nitrile compound,safe in humans,inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation[J/OL].Proc Natl Acad Sci U S A,2018,115(7):E1530-E1539.DOI:10.1073/pnas.1716095115.
[18] Huang Y,Jiang H,Chen Y,et al.Tranilast directly targets NLRP3 to treat inflammasome-driven diseases[J/OL].EMBO Mol Med,2018,10(4):e8689.DOI:10.15252/emmm.201708689.
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[20] Rathinam V A K,Zhao Y,Shao F.Innate immunity to intracellular LPS[J].Nat Immunol,2019,20(5):527-533.
[21] Yi Y S.Regulatory roles of the caspase-11 non-canonical inflammasome in inflammatory diseases[J/OL].Immune Netw,2018,18(6):e41-e41.DOI:10.4110/in.2018.18.e41.
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[23] Lee H E,Yang G,Kim N D,et al.Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester:a novel strategy to treat acute gout[J/OL].Sci Rep,2016,6:38622.DOI:10.1038/srep38622.
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[25] Kwak S B,Koppula S,In E J,et al.Artemisia extract suppresses NLRP3 and AIM2 inflammasome activation by inhibition of ASC phosphorylation[J/OL].Mediators Inflamm,2018,2018:6054069.DOI:10.1155/2018/6054069.
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[31] Han X,Sun S,Sun Y,et al.Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy:implications for Parkinson disease[J].Autophagy,2019 Apr 9:1-22.DOI:10.1080/15548627.2019.1596481.[Epub ahead of print].
[32] Ge Y,Xu X,Liang Q,et al.α-Mangostin suppresses NLRP3 inflammasome activation via promoting autophagy in LPS-stimulated murine macrophages and protects against CLP-induced sepsis in mice[J].Inflamm Res,2019,68(6):471-479.
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[34] Pal A,Neo K,Rajamani L,et al.Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides[J/OL].Sci Rep,2019,9(1):4913.DOI:10.1038/s41598-019-41211-3.
[35] Abdullaha M,Mohammed S,Ali M,et al.Discovery of quinazolin-4(3H)-ones as NLRP3 inflammasome inhibitors:Computational design,metal-free synthesis,and in vitro biological evaluation[J].J Org Chem,2019,84(9):5129-5140.