期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

parkin对AD转基因果蝇模型的神经保护作用及其作用机制的研究 被引量：2

Research on neuroprotective role of parkin in AD transgenic Drosophila models and its effect mechanism of parkin
下载PDF
导出
摘要 目的探讨parkin在阿尔茨海默病(AD)发病机制中的作用。方法利用经典的GAL4/UAS系统,选用nina EGAL4启动子,将突变位点在R406W处的Tau蛋白在果蝇复眼内选择性表达,构建nina E-GAL4/UAS系统AD转基因果蝇模型。然后分别在敲除和不敲除线粒体分裂蛋白Drp1情况下,使parkin在AD转基因果蝇模型中表达。结果 parkin明显抑制了AD转基因果蝇模型复眼视网膜光感受神经元变性,而在Drp1被敲除后,parkin的保护作用效果明显减弱。结论 parkin对AD转基因果蝇模型具有神经保护作用,而这种神经保护作用可能需要依赖线粒体分裂蛋白Drp1的功能。 Objective To confer the influence of parkin on pathogenesis of AD.Methods Here,using the classical model of GAL4/UAS system,and ninaE-GAL4 / UAS system AD transgenic Drosophila models were constructed by using the promoter ninaE-GAL4,which drive hTauR406w protein （Tau protein which mutation site is at R406W）,selectively expression in cells of Drosophila eyes.Then,parkin protein was expressed in AD transgenic Drosophila models by genetic methods with or without in a background of mitochondrial fission protein of Drp1.Results Expression of parkin notably suppresses the neurotoxicity of retinal photoreceptors in AD transgenic Drosophila models.Moreover,RNAi knockdown of Drp1 significantly parkin＇s protection against AD Drosophila.Conclusion It is confirmed that expression of parkin could protect AD transgenic Drosophila models,and the protection role of parkin is Drp1-dependent,maybe.
作者 黄强 李琼 韦荔莉 崔莹 胡艳梅 李清华
机构地区 桂林医学院附属医院神经内科
出处 《安徽医科大学学报》 CAS 北大核心 2014年第12期1735-1738,共4页 Acta Universitatis Medicinalis Anhui
基金 国家自然科学基金(编号:81160163)
关键词 阿尔茨海默病 TAU PARKIN Drp1 果蝇 Alzheimer＇s disease Tau parkin Drp1 transgenic Drosophila models
分类号 R741 [医药卫生—神经病学与精神病学]
  • 相关文献

参考文献12

  • 1Shea Y F, Chu L W, Mok M Y, et al. Amyloid beta 1-42 and tau in the cerebrospinal fluid of renal failure patients for the diagnosis of Alzheimer's disease [ J]. J Nephrol,2014,27 (2) :217 - 20.
  • 2Castello N A, Nguyen M H,Tran J D, et al. 7,8-Dihydroxyflavone, a small molecule trkB agonist, improves spatial memory and in- creases thin spine density in a mouse model of alzheimer disease- like neuronal loss [ J 1. PLoS One,2014,9 ( 3 ) : e91453.
  • 3Menndez J, Rodriguez-Navarro J A, Solano R M, et al. Suppressionf parkin enhances nigrostriatal and motor neuron lesion in mice o- ver-expressing humma-mutated tau protein [ J ]. Hum Mol Genet, 2006, 15(13) : 2045 -58.
  • 4Farter M, Chan P, Chen R, et al. Lewy bodies and parkinsonism in families with parkin mutations[ J ]. Ann Neural, 2001,50 (3) : 293 - 300.
  • 5Morales B, Martinez A, Gonzalo I, et al. Steele-richardson-olsze- wski syndrome in a patient with a single C212Y mutation in the parkin protein [ J ]. Mov Disord ,2002,17 (6) : 1374 - 80.
  • 6Trempe J F, Fon E A. Structure and function of parkin, PINKI, and [ J], the three musketeers of neuroproteetion [ J ]. Front Neu- ro1,2013 ,4 :38.
  • 7范珺.老年流行病[M].北京:军事医学科学出版,2008,179-85.
  • 8Kitao Y, Imai Y, Ozawa K, et al. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic retic- ulum stress and dopamine toxicit y, which is enhanced under con- dition of parkin inactivation[J]. Hum Mol Genet, 2007, 16( 1 ) : 50 - 60.
  • 9Miiller-Rischart A K, Pilsl A, Beaudette P, et al. The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiq- uitination of NEMO[J]. Mol Ce11,2013,49(5) :908 -21.
  • 10McLelland G L, Soubannier V, Chen C X,et al. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control[J]. EMBO J,2014,33 (4) : 282 -95.

同被引文献52

  • 1Kraft C,Peter M,Hofmann K. Selective autophagy: ubiquitin -mediated recognition and beyond [ J ]. Nat Cell Biol, 2010,2(9): 836 -841.
  • 2Wang H, Song P, Du L, et al. Parkin ubiquitinates Drpl for pro-teasome - dependent degradation : Implication of dysregulated mito-chondrial dynamics in Parkinsonr s disease [ J]. J Biol Chem,2011,286(13) : 11649 -11658.
  • 3Myeku N, Metcalfe MJ, Huang Q, et al. Assessment of protea-some impairment and accumulation/ aggregation of ubiquitinatedproteins in neuronal cultures[ J]. Methods Mol Biol, 2011, 793 :273 -296.
  • 4Chang C, Wu G, Gao P,et al. Upregulated Parkin expressionprotects mitochondrial homeostasis in DJ - 1 konckdown cells andcells overexpressing the DJ - 1 L166P mutationf J]. Mol Cell Bio-chem, 2014,387(1/2) : 187 -195.
  • 5Palacino JJ, Sagi D,Goldberg MS, et al. Mitochondrial dysfunc-tion and oxidative damage in parkin - deficient mice [ J ]. J BiolChem, 2004,279(18) : 18614-18622.
  • 6Wong YC, Holzbaur EL. Temporal dynamics of PARK2/parkinand OPTN/optineurin recruitment during the mitophagy of damagedmitochondria[ J]. Autophagy, 2015, 11(2) : 422 -424.
  • 7Roy M, Kageyama Y, Iijima M,et al. PARK2/Parkin becomescritical when DNMIL/Drpl is absent [ J ]. Autophagy, 2015,11(3); 573 -574.
  • 8Greenamyre JT, Cannon JR, Drolet R, et al. Lessons from the ro-tenone model of Parkinson's disease[ J]. Trends Pharmacol Sci.
  • 9Tanaka A. Parkin - mediated selective mitochondrial autophagy,mitophagy : Parkin purges damaged organelles from the vital mito-chondrial network [J]. FEBS Lett, 2010,584(7) : 1386 -1392.
  • 10McLelland GL, Soubannier V, Chen CX, et al. Parkin andPINK1 function in a vesicular trafficking pathway regulating mito-chondrial quality control [ J]. EMBO J, 2014, 33 (4): 282 -295.

引证文献2

二级引证文献6

安徽医科大学学报
2014年 第12期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部