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| 1 | 肌萎缩性侧索硬化蛋白激活小胶质细胞NLRP3炎性小体显示文摘小胶质细胞NLRP3炎性小体激活正在成为神经退行性变过程中神经炎症的关键因素。诸如β-淀粉样蛋白和α-突触核蛋白之类的致病性蛋白质聚集体触发小胶质NLRP3激活,从而导致半胱天冬酶-1激活和IL-1β的分泌。在小鼠肌萎缩性侧索硬化症(ALS)的SOD1G93A模型中,半胱天冬酶-1和IL-1β均促进疾病进展,提示小胶质NLRP3在该进程中发挥作用。然而先前的研究表明,SOD1G93A小鼠小胶质细胞不表达NLRP3,SOD1G93A蛋白在小胶质细胞中产生独立于NLRP3的IL-1β。本研究论证了使用Nlrp3-GFP基因敲入小鼠,在SOD1G93A小鼠中小胶质细胞表达NLRP3。本研究显示聚集和可溶性SOD1G93A均可激活小鼠原代小胶质细胞中的炎性小体,导致半胱天冬酶-1和IL-1β裂解,ASC斑点形成以及呈剂量和时间依赖性的IL-1β分泌。重要的是,SOD1G93A无法从缺乏Nlrp3的小胶质细胞或者用特异性NLRP3抑制剂MCC950预处理的小胶质细胞中诱导IL-1β分泌,从而证实NLRP3是介导SOD1诱导的小胶质细胞IL-1β分泌的关键炎症小体复合物。在TDP-43Q331K ALS小鼠模型中也观察到小胶质NLRP3上调,TDP-43野生型和突变蛋白亦可以NLRP3依赖性的方式激活小胶质炎性小体。从机制上讲,本研究确定了活性氧簇和ATP的生成是SOD1G93A介导的NLRP3激活所需的关键事件。总之,本研究的数据表明ALS小胶质细胞表达NLRP3,而病理ALS蛋白激活小胶质NLRP3炎性小体。因此,NLRP3抑制可能是阻止小胶质细胞神经炎症和ALS疾病进展的潜在治疗方法。 | Vandana Deora John D Lee Eduardo AAlbornoz Luke McAlary Cyril J Jagaraj Avril A B Robertson Julie D Atkin Matthew A Cooper Kate Schroder Justin J Yerbury Richard Gordon Trent MWoodruff 杜一星(编译) | 2020 | 神经损伤与功能重建2020，15，9： | 13 |
| 2 | Detection and analysis of hairpin II,an essential metastable structural element in viroid replication intermediates显示文摘 | Riesner D | 2002 | Nucleic Acids Res2002，30，： | 1 |
| 3 | 显示文摘 | Schroder D K | 1982 | IEEE Trans Electron Devices1982，29，： | 1 |
| 4 | Wavefront-supported photorefractive keratectomy: 12-month follow-up 显示文摘 | Dausch D Dausch S Schroder E | 2003 | J Refract Surg2003，19，4： | 1 |
| 5 | Reliability prediction for inverters in hybrid electrical vehicles 显示文摘 | HIRSCHMANN D TISSEN D SCHRODER S | 2007 | IEEE Transactions on Power Electronics2007，22，6： | 1 |
| 6 | Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages 显示文摘 | AHRENS M ANKENBAUER T SCHRODER D | 1993 | DNA Cell Biol1993，12，10： | 1 |
| 7 | Sleep characteris- tics, sleep problems, and associations to quality of life among psyehotherapists显示文摘 | SCHLARB A A REIS D SCHRODER A | 2012 | Sleep Disorders2012，，12： | 1 |
| 8 | Effect of immediate postoper-ative enteral nutrition on body, composition, muscle function andwound healing 显示文摘 | Schroder D Klein S Kinney J | 1991 | JPEN1991，15，4： | 1 |
| 9 | Chronic periodontal disease is associated with single - nucleotide polymorphisms of the human TLR - 4 gene 显示文摘 | SCHRODER N W MEISTER D WOLFF V | 2005 | Genes Immun2005，6，5： | 1 |
| 10 | Elastic waves interacting with buried land mines: A study using the FDTD method显示文摘 | Scott W Jr Larson G D | 2002 | IEEE Transactions on Geoscience and Remote Sensing2002，40，： | 1 |
| 11 | 显示文摘 | Schulz D Schroder W | 1996 | Journal of Crystal Growth1996，163，： | 1 |
| 12 | Candidosis and aspergillosis as autopsy findings from 1994 to 2003 显示文摘 | Schwesinger G Janghans D Schroder G | 2005 | Mycoses2005，48，3： | 1 |
| 13 | LIMP-2 is a receptor for lysosomal mannose-6- phosphate-independent targeting of beta-glucocerebrosidase显示文摘 | Reczek D Schwake M Schroder J | 2007 | Cell2007，131，4： | 1 |
| 14 | Reliability prediction for inverters in hybrid electrical vehicles显示文摘 | HIRSCHMANN D TISSEN D SCHRODER S et aI | 2007 | IEEE Transcations on Power Electronics2007，22，6： | 1 |
| 15 | Fast-track surgery : procedure specific aspects and future direction 显示文摘 | Ansari D Gianotti L Schroder J | 2013 | Langenbecks Arch Surg2013，398，1： | 1 |
| 16 | Ecbogenicity of the substantia nigra:association with increased iron content and maker for susceptibility to nigrostriatal injury 显示文摘 | Berg D Roggendorf W Schroder U | 2002 | Arch Neurol2002，59，6： | 1 |
| 17 | Non-cultured adipose-derived CD45' side population cells are enriched for progenitors that give rise to myofibres in vivo显示文摘 | Andersen D C Schroder H D Jensen C H | 2008 | Exp Cell Res2008，314，16： | 1 |
| 18 | Microcirculatory changes associated with gastric tube formation in the pig显示文摘 | Schroder W Beckurts KT Stahler D | 2002 | Eur Surg Res2002，34，6： | 1 |
| 19 | Two-state reactivity as a new concept in organometallic chemistry 显示文摘 | SCHRODER D SHAIK S SCHWARZ H | 2000 | AccChem Res2000，33，3： | 1 |
| 20 | Interferon - 3' : An Overview of Signals, Mechanisms and Functions 显示文摘 | Schroder K Hertzog P J Ravasi T Hume D A | 2004 | J Leukoc Biol2004，75，2： | 1 |
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