Genetics and Developmental Biology Laboratory, Department of Biological Sciences and Biotechnology, Institute of Advanced Research (IAR), Koba, Gandhinagar, Gujarat 382426, India.
Genetics and Developmental Biology Laboratory, Department of Biological Sciences and Biotechnology, Institute of Advanced Research (IAR), Koba, Gandhinagar, Gujarat 382426, India
Biol Open. 2020 Sep 3;9(9):bio049569. doi: 10.1242/bio.049569.
Miro (mitochondrial Rho GTPases), a mitochondrial outer membrane protein, facilitates mitochondrial axonal transport along the microtubules to facilitate neuronal function. It plays an important role in regulating mitochondrial dynamics (fusion and fission) and cellular energy generation. Thus, Miro might be associated with the key pathologies of several neurodegenerative diseases (NDs) including Alzheimer's disease (AD). In the present manuscript, we have demonstrated the possible genetic interaction between Miro and AD-related genes such as , and in Ectopic expression of , and induced a rough eye phenotype, defects in phototaxis and climbing activity, and shortened lifespan in the flies. In our study, we have observed that overexpression of improves the rough eye phenotype, behavioral activities (climbing and phototaxis) and ATP level in AD model flies. Further, the improvement examined in AD-related phenotypes was correlated with decreased oxidative stress, cell death and neurodegeneration in overexpressing AD model flies. Thus, the obtained results suggested that genetically interacts with AD-related genes in and has the potential to be used as a therapeutic target for the design of therapeutic strategies for NDs.This article has an associated First Person interview with the first author of the paper.
Miro(线粒体 Rho GTPases)是一种线粒体外膜蛋白,可促进线粒体沿微管的轴突运输,从而促进神经元功能。它在调节线粒体动力学(融合和裂变)和细胞能量产生方面发挥着重要作用。因此,Miro 可能与包括阿尔茨海默病(AD)在内的几种神经退行性疾病(NDs)的关键病理学有关。在本手稿中,我们已经证明了 Miro 与 AD 相关基因(如 、 和 )之间可能存在遗传相互作用。异位表达 、 和 会诱导果蝇出现粗糙眼表型、光趋性和攀爬活动缺陷以及寿命缩短。在我们的研究中,我们观察到过表达 可改善 AD 模型果蝇的粗糙眼表型、行为活动(攀爬和光趋性)和 ATP 水平。此外,在 AD 相关表型中观察到的改善与 AD 模型果蝇中氧化应激、细胞死亡和神经退行性变的减少相关。因此,研究结果表明 与 AD 相关基因在 中存在遗传相互作用,并具有作为设计 NDs 治疗策略的治疗靶点的潜力。本文有一篇与该论文第一作者的第一人称访谈。