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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 | Ownership and organizational performance: a comparison of technical efficiency across hospital types 显示文摘 | Ozcan Y A Luke R D Haksever G | 1992 | Medical Care1992，30，9： | 1 |
| 3 | Declining rates of physical activity in the United States: What are the contribu- tors? 显示文摘 | BROWNSON R C BOEHMER T K LUKE D A | 2005 | Annu Rev Public Health2005，26，： | 1 |
| 4 | Ownership and organizational performance:A comparison of technical effi- ciency across hospital types显示文摘 | OzcanYasar A Roice D Luke Cengiz Haksever | 1992 | Medical Care1992，30，9： | 1 |
| 5 | New criteria for diagnosis of infective endoearditis: utilization of specific echocardiographic findings: Duke Endocarditis Service显示文摘 | DURACK D T LUKES A S BRIGHT D K | 1994 | Am J Med1994，96，： | 1 |
| 6 | The hydrodynamic ram pressure generated by spherical projectiles 显示文摘 | PETER J D LUKE A S NORMAN T | 2009 | International Journal of Impact Engineering2009，36，： | 1 |
| 7 | Pediatric orogastric and nasogastric tubes: a new formula evaluated显示文摘 | Klasner A E Luke D A Scalzo A J | 2002 | Ann Emerg Med2002，39，3： | 1 |
| 8 | Ownership and organizational performance显示文摘 | Ozcan Yasar A Roice D Luke Cengiz Haksever | 1992 | A comparison of technical efficiency across hospital types Medical Care1992，30，9： | 1 |
| 9 | Phylogeny of Trypanosomesas inferred from the small and large subunit rRNAs:Implieations for the evolution of parasitism in the Trypanosomatid protozoa 显示文摘 | Maslov D A Lukes J Jirku M | 1996 | Mol Biochem Parasitol1996，75，： | 1 |
| 10 | Methylisocyanate:an evaluation of in vivo cytogeneticactivity显示文摘 | Tice R R Luke C A Shelby M D | 1987 | Environmental Mutagenesis1987，，9： | 1 |
| 11 | Heat transfer and size distribution of active nucleation sites in boiling propane outside a tude 显示文摘 | LUKE A GORENFLO D | 2000 | International Journal Thermal Science2000，39，： | 1 |
| 12 | Perceptions of neighborhood environment for physical activity,Is it 'Who you are ' or 'Where you live'显示文摘 | BOSLAUGH S E LUKE D A BROWNSON R C | 2004 | J Urban Health2004，81，4： | 1 |
| 13 | Boiling phenomena with surfactants and polymeric additive: a state-of-the-art review 显示文摘 | Cheng L Mewes D Luke A | 2007 | International Journal of Heat and Mass Transfer2007，50，1314： | 1 |
| 14 | Getting the big picture in community science:methods that capture context显示文摘 | Luke D A | 2005 | American Journal of Community Psychology2005，35，34： | 1 |
| 15 | Inhibition of 2A-mediated ' cleavage' of certain artificial polyproteins bearing Nterminal signal sequences显示文摘 | de Felipe P Luke G A Brown J D | | 0，，02： | 1 |
| 16 | Colostomy irrigation can enhance quality of life after abdomen operineal resection of the rec- tum显示文摘 | Luke D Ebanks A Bowley D | 2012 | Colorectal Disease2012，14，6： | 1 |
| 17 | Systems science methods in pub-lic health:dynamics,networks,and agents显示文摘 | Luke D A Stamatakis K A | 2012 | Annu Rev Pub-lic Health2012，，： | 1 |
| 18 | A portable X-ray fluorescence instrument for analyzing dust wipe samples for lead: Evaluation with field samples 显示文摘 | Sterling D A Lewis R D Luke D A Shadel B N | 2000 | Environmental Research2000，83，2： | 1 |
| 19 | Thermal ex- pansion in 3d-metal Prussian Blue Analogs 显示文摘 | Sourav A Luke L D Monika H | 2011 | Jour- nal of Solid State Chemistry2011，184，11： | 1 |
| 20 | Forty years of secondhand smoke research: The gap between discovery and delivery 显示文摘 | Harris J K Luke D A Zuckerman R B | 2009 | American Journal of Preventive Medicine2009，36，6： | 1 |
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