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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 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 3 | The valid use of utility in adaptive real-time systems 显示文摘 | PRASAD D BURNS A ATKINS M | 2003 | Real-Time System2003，25，23： | 1 |
| 4 | Regenerating functional myocardium: improved perfolrnance after skeletal myoblast transplantation 显示文摘 | Taylor D A Atkins B Z Hungspreugs P | 1998 | Nat Med1998，4，8： | 1 |
| 5 | Assessment of the ecological potential of mine-water treatment wetlands using a baseline survey of macroinvertebrate communities显示文摘 | Batty L C Atkin L Manning D A | 2005 | Environmental Pollution2005，138，： | 1 |
| 6 | Effects of pO(2) on the formation and status of leghaemoglobin 显示文摘 | Dakora D F Appleby C A Atkins C A | 1991 | Plant Physiology1991，95，： | 1 |
| 7 | Metal particles stimulate expression of regulators of osteoclast development including osteoclast differentiation factor (RANKL/TRANCE),osteoprotegerin macrophage colony stimulating factor显示文摘 | HAYNES D R POTTER A E ATKINS G J | 1999 | Trans Orthop Res Soc1999，24，3： | 1 |
| 8 | Chemical sequence control of beta-sheet assembly in macromolecular crystals of periodic polypeptides显示文摘 | Krejchi M T Atkins E D T Waddon A J | 1994 | Science1994，265，： | 1 |
| 9 | Phase Ⅱ study of carboplatin, irinotecan, and thalidomide in patients with ad- vanced non - small cell lung cancer 显示文摘 | Miller A A Case D Atkins J N | 2006 | J Thorac Onco2006，1，8： | 1 |
| 10 | Grading quality of evidence and strength of recommendations 显示文摘 | Atkins D Best D Briss P A | 2004 | BMJ2004，328，7454： | 1 |
| 11 | Regenerating functional myocardium: improved performance after skelectal myoblast transplantation显示文摘 | Atkins B Z Hungspreugs P | 1998 | Nat Med1998，4，： | 1 |
| 12 | A note on joint opti mization of maintenance and inventory显示文摘 | ARMSTRONG M J ATKINS D A | 1998 | IIE Transac- tions1998，30，2： | 1 |
| 13 | Grading quality of evi- dence and strength of recommendations 显示文摘 | Atkins D Best D Briss P A | 2004 | BMJ2004，328，7454： | 1 |
| 14 | PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis 显示文摘 | Barish G D Atkins A R Downes M | 2008 | Proc Natl Acad Sci USA2008，105，11： | 1 |
| 15 | Hy- brid metaheuristics to aid runway scheduling at Lon- don heathrow airport显示文摘 | Atkin J A D Burke E K Greenwood J S | 2007 | Transport Sci2007，41，： | 1 |
| 16 | PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis显示文摘 | Barish G D Atkins A R Downes M | 2008 | Proc Natl Acad Sci U S A2008，105，11： | 1 |
| 17 | Event specific drinking among college students显示文摘 | Neighbors C Atkins D C Lewis M A | 2011 | Psychol Addict Behav2011，25，4： | 1 |
| 18 | Assessment of the ecologicalpotential of mine-water treatment wetlands using a baseline survey ofmacroinvertebrate communities显示文摘 | Batty L C Atkin L Manning D A C | 2005 | Environmental Pollution2005，138，： | 1 |
| 19 | Ion circulation via phloem and xylem between root and shoot of noclnlalecl while lupin显示文摘 | Jescheke W D Atkins L A Pate J S | 1985 | J Plant Physiol1985，117，： | 1 |
| 20 | Characterisation of electrospun polystyrene scaffolds for three-dimensional in vitro biological studies 显示文摘 | S C Baker N Atkin P A Gunning N Granville K Wilson D Wilson J Southgate | 2006 | Biomaterials2006，27，： | 1 |
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