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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 | Vertical distribution and temporal variation of dissolved organic carbon in the North-Western Mediterranean Sea 显示文摘 | Copin-Montogut G Avril B | 1993 | Deep Sea Research Part Ⅰ: Oceanographic Research Papers1993，40，10： | 1 |
| 3 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 Southwest Monsoon显示文摘 | Coble P G Del Castillo C E Avril B | 1998 | Deep-Sea Res PT II1998，45，1011： | 1 |
| 4 | Starch Granule-AssociatedProteins and Polypeptides: A Review显示文摘 | M B Paul Avrill 6 France | 2001 | Starch/Starke2001，53，10： | 1 |
| 5 | Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell earcinomas from DNA repair-deficient xeroderma pigmentosum patients显示文摘 | Couve-Privat S Bouadjar B Avril MF | 2002 | Cancer Res2002，62，24： | 1 |
| 6 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 Southwest Monsoon显示文摘 | COBLE P G DEL CASTILLO C E AVRIL B | 1998 | Deep-Sea Res Ⅱ1998，45，： | 1 |
| 7 | Correlation of the expression of acrB and the regulatory genes marA,soxS and ramA with antimicrobial resistance in clinical isolates of Klebsiella pneumoniae endemic to New York City显示文摘 | Simona B David L Avrille G | 2009 | J Antimicrob Chemother2009，64，2： | 1 |
| 8 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 Southwest Monsoon 显示文摘 | COBLE P G DEL CASTILLO C E AVRIL B | 1998 | Deep-Sea Research II1998，45，1011： | 1 |
| 9 | Tribological performance of α-Fe (Cr)-Fe2 B-FeB and α-Fe (Cr)-h- BN coatings obtained by laser mehing 显示文摘 | Avril L Courant B Hantzpergue J J | 2006 | Wear2006，260，： | 1 |
| 10 | Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients 显示文摘 | Couve-Privat S Bouadjar B Avril MF | 2002 | Cancer Res2002，62，24： | 1 |
| 11 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 Southwest Monsoon显示文摘 | Coble P G Del Castillo C E Avril B | 1998 | Deep-Sea Res1998，245，： | 1 |
| 12 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 southwest monsoon 显示文摘 | COBLE P G DEL CASTILLO C E AVRIL B | 1998 | Deep-Sea Research Ⅱ1998，45，： | 1 |
| 13 | Opposite regulation of myc and p2 l wafl transcription by STAT3 proteins显示文摘 | Barre B Avril S Coqueret O | 2003 | J Biol Chem2003，278，5： | 1 |
| 14 | Tri- bological performance of a-Fe(Cr)-Fe2 B-FeB and a-Fe (Cr)-h-BN coatings obtained by laser melting 显示文摘 | AVRIL L COURANT B HANTZPERGUE J J | 2006 | Wear2006，，260： | 1 |
| 15 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 Southwest Monsoon 显示文摘 | COBLE P G DEL CASTILLO C E AVRIL B | 1998 | Deep Sea Research Part II: Topical Studies in Oceanography1998，45，1011： | 1 |
| 16 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 South west Monsoon显示文摘 | COBLE P G DEL CASTILLO C E AVRIL B | 1998 | Deep-Sea Research Part II1998，45，1011： | 1 |
| 17 | Fast Collision Culling in Large-scale Environments Using GPU Mapping Function显示文摘 | Avril Q Gouranton V Amaldi B | | 0，，06： | 1 |
| 18 | Overview of cellularimmunotherapy for patients with glioblastoma 显示文摘 | Vauleon E Avril T Collet B | 2010 | Clin DevImmunol2010，2010，： | 1 |
| 19 | Overview of cellular immunotherapy for patients with glioblastoma显示文摘 | Vauleon E Avril T Collet B | 2010 | Clin Dev Immunol2010，2010，68： | 1 |
| 20 | Distribution and optical properties of CDOM in the Arabian Sea during the 1995 South West Monsoon显示文摘 | COBLE P G DELCASTILLO C E AVRIL B | 1998 | Deep-Sea Research Part Ⅱ1998，45，1011： | 1 |
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