沉默信息调节因子2对SCA3/MJD转基因果蝇的神经保护作用及其与自噬的相关性研究  

The Neuro-protective Role of Sir2 in The Process of Neuro-degeneration of The SCA3/MJD Model Flies is Dependent on Autophagy Function

作　　者：曾爱源[1] 朱惊雷[1] 洪亢亢[1] 张灼华[2] 段然慧[2] 孙莉[1] 刘承伟[1] 魏小莉[1] 韦荔莉[1] 陈梅玲[1] 林小慧[1] 陈薇[1] 李清华[1] 

机构地区：[1]桂林医学院附属医院神经内科,桂林541001 [2]中南大学医学遗传学国家重点实验室,长沙410078

出　　处：《生物化学与生物物理进展》2012年第3期250-256,共7页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(30960112,81160163);广西自然科学基金(0991259,0899014);广西卫生厅课题(Z2007197);桂林市科技与开发课题(20080707)资助项目~~

摘　　要：为探讨沉默信息调节因子2(Sir2)在SCA3/MJD发病机制中的作用.选用GMR-GAL4和Nrv2-GAL4驱动子,利用经典的GAL4-UAS系统,将含有78个CAG重复扩增的ataxin-3蛋白片段(MJDtr-Q78)分别在果蝇眼睛和运动神经元内选择性表达,构建GMR-GAL4/UAS和Nrv2-GAL4/UAS系统SCA3/MJD转基因果蝇模型,然后分别在抑制和不抑制自噬的情况下,使Sir2在SCA3/MJD转基因果蝇眼睛和运动神经元内过表达.结果发现,Sir2过表达明显抑制了SCA3/MJD转基因果蝇眼睛视网膜光感受神经元变性,显著改善了果蝇运动能力,而在自噬被抑制后,Sir2的作用效果明显减弱,表明Sir2对SCA3/MJD转基因果蝇具有神经保护作用,而这种神经保护作用需要依赖自噬的功能.To confer the influence of Sir2 on pathogenesis of SCA3/MJD.GMR-GAL4 and Nrv2-GAL4 system SCA3/MJD transgenic Drosophila models were constructed by using the promoter GMR-GAL4 and Nrv2-GAL4 which drive target selective gene expression in cells of the developing eyes and motor neurons,respectively.Then,Sir2 protein was overexpressed in SCA3/MJD transgenic Drosophila models by genetic methods with or without in a background of RNAi knockdown of Atg7.Overexpression of endogenous Drosophila Sir2 not only notably suppresses the neurotoxicity of MJDtr-Q78 protein,but also significantly improves the movement ability of flies.Moreover,RNAi knockdown of Atg7 significantly Sir2＇s protection against SCA3/MJD Drosophila.We confirmed that overexpression of Sir2 could protect SCA3/MJD Drosophila models,and the protection role of Sir2 on SCA3/MJD Drosophila models is autophagy-dependent.

关 键 词：遗传性脊髓小脑性共济失调3型 沉默信息调节因子2(Sir2) 转基因果蝇 自噬 神经保护 

分 类 号：R74[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学]