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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 | Annexin Ⅱ regulates fibrin homeostasis and neo-angiogenesis in vivo 显示文摘 | Ling Q Jacovina AT Deora A | 2004 | J Clin Invest2004，113，1： | 1 |
| 3 | An ICAM-1 like cell adhesion moleculer is responsible for CD34 positive haemopoietic stem cells adhesion tobone marrow stroma 显示文摘 | Rao SGA Chitnis VS Deora A | 1996 | Cell Biol Inv1996，20，： | 1 |
| 4 | Expectation-based quality of service assessment显示文摘 | Deora V Shao Jianhua Gray W A | 2006 | International Journal on Digital Libraries2006，6，3： | 1 |
| 5 | Reverse transcriptase-mediated tropism switching in Bordetella bacteriophage 显示文摘 | Liu M S Deora R Doulatov S R Gingery M Eiserling F A Preston A Maskell D J Simons R W Cotter P A Parkhill J | 2002 | Science2002，295，5562： | 1 |
| 6 | Application of deep belief networks for natural language understanding显示文摘 | SARIKAYA R HINTON G E DEORAS A | 2014 | IEEE/ACM transactions on audio speech and language processing2014，22，4： | 1 |
| 7 | Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo显示文摘 | Ling Q Jacovina AT Deora A | 2004 | J Clin Invest2004，113，1： | 1 |
| 8 | Annexin li Medi- ates Plasminogen-l)ependent Matrix Invasion by Human Monocytes: Enhanced Expression hy Macrophages 显示文摘 | Brownstein C Deora A B Jacovina A T | 2004 | Blood2004，103，： | 1 |
| 9 | Annexin II regulates fibrin homeostasis and neo-angiogenesis in vivo显示文摘 | Ling Q Jacovina AT Deora A Febbraio M Simantov R Silver-stein RL | 2004 | J Clin Invest2004，113，1： | 1 |
| 10 | Annexin Ⅱ regulates fibrin homeostasis and neoangiogenesis in vivo显示文摘 | Ling Q Jacovina A Deora A | 2004 | J Clin Invest2004，113，1： | 1 |
| 11 | Application of deep belief networks for natural language understanding 显示文摘 | SARIKAYA R HINTON G E DEORAS A | 2014 | IEEE Transactions on Audio Speech and Language Processing2014，22，4： | 1 |
| 12 | Application of deep belief net- works for natural language understanding 显示文摘 | Sarikaya R Hinton G E Deoras A | 2014 | I EEE/ACM Trans on Audio Speech and Language Processing2014，22，4： | 1 |
| 13 | Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo显示文摘 | Ling Q Jacovina AT Deora A etal | 2004 | J Clin Invest2004，113，： | 1 |
| 14 | Ultrasound for improved crystallisation in food processing显示文摘 | DEORA N S MISRA N N DESWAL A | 2013 | Food Engineering Reviews2013，5，1： | 1 |
| 15 | Annexin Ⅱ regulates fibrin homeostasis and neoangiogenesis in vivo显示文摘 | Ling Q Jacovina AT Deora A | 2004 | J Clin Invest2004，113，1： | 1 |
| 16 | Application of deep belief networks for natural language understanding 显示文摘 | Sarikaya R Hinton G E Deoras A | 2014 | IEEE/ACM Transactions on Audio Speech and Language Processing2014，22，4： | 1 |
| 17 | Mechanisms regulating tissue- specific polarity of monocarboxylate transporters and their chaper- one CD147 in kidney and retinal epithelia显示文摘 | Deora A A Philp N Hu J | 2005 | Proc Natl Acad Sci U S A2005，102，16： | 1 |
| 18 | Down-modulation of p210 bcr/abl induces apoptosis/differentiation in K562 leukemic blast cells显示文摘 | Deora A B Miranda M B Rao S G | 1997 | Tumor1997，83，4： | 1 |
| 19 | Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia显示文摘 | Deora A A Philp N Hu J Bok D Rodriguez-Boulan E | 2005 | Proc Natl Acad Sci USA2005，102，16： | 1 |
| 20 | New concepts in fibrinolysis and angiogenesis显示文摘 | Deora A | 2000 | Curr Atheroscler Rep2000，2，5： | 1 |
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