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帕金森病(PD)是以黑质致密部多巴胺神经元选择性减少和胞浆内路易小体的形成为特征的神经退行性疾病。研究发现,PTEN诱导激酶1(PINK1)基因突变导致家族性早发型帕金森病的发生。在转基因果蝇中,PINK1功能丢失导致间接飞行肌缺陷,线粒体结构、功能障碍,多巴胺神经元丢失。本研究在PINK1突变PD转基因果蝇中,进行发动蛋白相关蛋白1(Drp1)过表达和敲低,探索Drp1对PD转基因果蝇的保护作用及其可能机制。本研究选用MHC-Gal4/UAS系统的PD转基因果蝇模型,特异性启动PINK1B9基因于果蝇肌肉组织中表达;运用Drp1基因过表达和RNA干扰干预PINK1B9转基因果蝇,研究其对PD转基因果蝇的作用。结果显示,不论过表达Drp1还是Drp1敲低均可挽救PINK1突变转基因果蝇,降低翅膀异常率,改善飞行能力,恢复间接飞行肌排列,调节线粒体形态,提高ATP生成量,上调NDUFS3蛋白表达水平。本文结果提示,Drp1的调控挽救PINK1突变转基因果蝇与线粒体呼吸链有关。
Parkinson’s disease (PD) is a neurodegenerative disease characterized by the selective reduction of dopaminergic neurons in the substantia nigra pars compacta and the formation of intracytoplasmic Lewy bodies. The study found that PTEN induced kinase 1 (PINK1) gene mutation leads to the occurrence of familial premature Parkinson’s disease. In transgenic Drosophila, loss of PINK1 function leads to indirect flight muscle defects, mitochondrial structure, dysfunction, and loss of dopamine neurons. In this study, knockdown of Drp1 was knocked down in PINK1 mutant PD transgenic Drosophila to explore the protective effect of Drp1 on PD transgenic Drosophila and its possible mechanism. In this study, MHC-Gal4 / UAS system of PD transgenic Drosophila model, specifically start PINK1B9 gene expression in Drosophila muscle tissue; use Drp1 gene overexpression and RNA interference interference PINK1B9 transgenic Drosophila study of PD transgenic Drosophila Role. The results showed that PINK1 mutant transgenic Drosophila could be rescued both overexpression of Drp1 and knockdown of Drp1, the abnormal rate of wings was reduced, the flight ability was improved, the flight alignment of indirect flight was restored, the morphology of mitochondria was regulated, the production of ATP was up-regulated and the expression of NDUFS3 protein was up-regulated. Our results suggest that the regulation of Drp1 rescues the PINK1 mutant transgene Drosophila and the mitochondrial respiratory chain.