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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 | In vivo lung lavage as an experimental model of the respiratory distress syndrome 显示文摘 | Lachmann B Robertson B Vogel J | 1980 | Acta Anaesthesiol Scand1980，24，3： | 2 |
| 3 | Symposium:carbohudrate methodology,metabolism,and nutritional implications in dairy cattle:Methods for dietary fibre,neutral detergent fibre,and nonstarch polysaccharides in relation to animal nutrition显示文摘 | Van Scest P J Robertson J B Lewis B A | 1991 | Journal of Dairy Science1991，74，10： | 1 |
| 4 | Destruction of cyanobacterial toxins by semiconductor photocatalysis显示文摘 | ROBERTSON P K J LAWTON L A MANCH B | 1997 | Chem Commun1997，，4： | 1 |
| 5 | Precision determination of lattice parameters and coefficients of thermal expansion of BiFeO3显示文摘 | Bucci J D Robertson B K James W J | 1972 | J Appl Cryst1972，5，： | 1 |
| 6 | Reservoir characteristics of Devonian cherts and their control on oil recovery: Dollarhide field, west Texas显示文摘 | Sailer A Ball B Robertson S | 2001 | AAPG Bulletin2001，85，1： | 1 |
| 7 | Investigation of the role of prolactin in the development and function of the lacrimal and harderian glands using genetically modified mice显示文摘 | McClellan KA Robertson FG Kindblom J Wennbo H Tornell J Bouchard B | 2001 | Invest Ophthalmol Vis Sci2001，42，1： | 1 |
| 8 | Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America显示文摘 | Arauz-Ruiz P Norder H Robertson B H Magnius L O | 2002 | J Gen Virol2002，83，8： | 1 |
| 9 | Isothermal hot deformation behavior of metasTable 13 titanium alloy Ti-IOV-2Fe-3A1 显示文摘 | Robertson D G McShane H B | 1997 | Marer Sci Technol1997，13，： | 1 |
| 10 | Design and construction of an active alignment demonstrator for a free-space optical interconnect显示文摘 | BOISSET G C ROBERTSON B HINTON H S | 1995 | Photonics Technology Letters1995，7，6： | 1 |
| 11 | A comparison of techniques for determining IVDMD at three time periods using the filter bag technique versus conventional techniques显示文摘 | Traxler M J Robertson J B Van Soest P J | 1995 | J Dairy Sci1995，78，1： | 1 |
| 12 | Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12 显示文摘 | ROBERTSON B H GRUBMAN M J WEDDELL G N | 1985 | J Virol1985，54，3： | 1 |
| 13 | A probotic strain of Vib- rio alginolyties effective in reducing diease caused by Aeromonas sal- monicida, Vibrio anguillrum and Vibrio ordali 显示文摘 | Austin B Stuckey L F Robertson P W | 1995 | J Fish Dis1995，18，： | 1 |
| 14 | A novel method for the efficient and selec- tive identification of 5-hydroxymethylcytosine in genomic DNA显示文摘 | ROBERTSON A B DAHL J A VAGBO C B | 2011 | Nucleic Acids Res2011，39，8： | 1 |
| 15 | Biophysical ac- tivity of an artificial surfactant containing an analogue of sur- factant protein (SP)-C and native SP B显示文摘 | Palmblad M Johansson J Robertson B | 1999 | Biochem J1999，，： | 1 |
| 16 | Effects of epidermal growth factor on hair growth in the mouse显示文摘 | Moore G P M Panaretto B A Robertson D M | 1981 | J Endocrinol1981，88，2： | 1 |
| 17 | Invivo hung lavage as an experimental model of the respiratory distress syndrome显示文摘 | Lachmann B Robertson B Vogel J | 1980 | Acta Anaesthesiol Scand1980，24，3： | 1 |
| 18 | Simplified design methods for pipelines subject to transverse and longitudinal soil movements显示文摘 | Brajani B Robertson P K Morgensten N R | 1995 | Canadian Geotechnical Journal1995，32，2： | 1 |
| 19 | Methods for dietary fiber,neutral detergent fiber and nonstarch polysaccharides in relation to animal nutrition显示文摘 | Van Soest P J Robertson J B Lewis B | 1991 | J Dairy Sci1991，74，： | 1 |
| 20 | Hydrogen peroxide enhanced photocatalytic oxidation of microcystin-LR using titanium dioxide 显示文摘 | Cornish B J P A Lawton L A Robertson P K J | 2000 | Applied Catalysis B: Environmental2000，25，1： | 1 |
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