Hsp22对SCA3/MJD转基因果蝇的神经保护作用研究

Research on Neuroprotective Role of Hsp22 in SCA3/MJD Transgenic Drosophila Models

为了探讨Hsp22在SCA3/MJD发病机制中的作用.选用GMR-GAL4和elav-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)分别在果蝇眼睛和神经系统选择性表达,构建GMR-GAL4/UAS和elav-GAL4/UAS系统SCA3/MJD转基因果蝇模型,然后利用遗传学方法和热休克反应使Hsp22在SCA3/MJD转基因果蝇眼睛和神经系统以不同水平过表达.结果表明,Hsp22过表达显著抑制了MJDtr-Q78蛋白的神经毒性,果蝇眼睛视网膜光感受神经元变性明显缓解,果蝇存活能力也显著提高.Hsp22对SCA3/MJD具有保护作用,增强Hsp22表达对SCA3/MJD可能是一种潜在的治疗方法.

To confer the influence of Hsp22 on pathogenesis of SCA3/MJD. GMR-GAL4 and elav-GAL4 system SCA3/MJD transgenic Drosophila models were constructed by using the promoter GMR-GAL4 and elav-GAL4 which drive target selective gene expression in developing eyes and neurons, respectively. Then, Hsp22 protein was overexpressed in SCA3/MJD transgenic Drosophila models at different levels by genetic methods and heat shock reaction. Overexpression of endogen Drosophila Hsp22 can notably suppress the neurotoxicity of MJDtr-Q78 protein, and the level of lisp22 expression was in consistent with rehabilitation for neurodegeneration of Drosophila eyes, and extension of Drosophila lifespan. It is firstly confirmed that expression of Hsp22 protects the SCA3/MJD from neurodegeneration on Drosophila models, which might contribute to a potential therapeutic effect on SCA3/MJD.