研究报告: 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

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．

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

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.