RT期刊文章SR电子T1缺乏Aprataxin损害线粒体功能的差别,通过对这些APE1 / NRF1 NRF2通路(S30.004)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP S30.004 VO 86是16补充A1 Beatriz Garcia-Di首页az A1 Emanuele巴萨A1 Andrea Balreira A1路易斯·洛佩兹A1萨特A1别克里希纳A1阿里Naini A1 Caterina Mariotti A1芭芭拉Castellotti A1卡塔琳娜州Quinzii Hirano年2016 UL //www.ez-admanager.com/content/86/16_Supplement/S30.004.abstract AB目的这项工作的目的是阐明机制缺乏辅酶q10共济失调动眼神经的失用症1型(AOA1),一个常染色体隐性神经退行性疾病,引起的突变APTX,哪个编码Aprataxin (APTX),一种蛋白质参与DNA strand-break修复。背景常染色体隐性小脑共济失调是异构神经退行性疾病。肌肉缺乏辅酶Q10(辅酶q),线粒体脂质,功能主要是线粒体呼吸链电子载体,作为抗氧化剂在细胞膜,据报道在13个(percnt)常染色体隐性小脑性共济失调患者的分子病因不明。我们和其他团体报道辅酶q缺乏肌肉和/或成纤维细胞APTX病人携带突变的原因常染色体隐性ataxia-oculomotor-apraxia 1 (AOA1)。患者部分应对补充辅酶q10,暗示缺辅酶q10在疾病的发病机理中的作用。然而,辅酶q10的机制缺乏二级APTX变异仍然是难以捉摸的。设计/方法AOA1不同患者的皮肤成纤维细胞的突变APTX和APTX-depleted海拉细胞,我们测量辅酶q10水平和生物合成,活细胞代谢、线粒体呼吸链酶活动,线粒体质量和线粒体DNA的拷贝数。我们分析了nuclear-mitochondrial通路调节线粒体基因表达。结果表明,APTX突变和耗尽细胞的线粒体功能障碍引起的减少APE1 NRF1 NRF2,他们的目标基因。生化和分子异常APTX突变和耗尽细胞中观察到被击倒的APE1戒律,,重要的是,由过度获救NRF1/2和药理老年病NRF2罗格列酮。 CONCLUSIONS. We showed that mitochondrial dysfunction, including CoQ deficiency, in AOA1, is caused by impairment of the APE1/NRF1/NRF2 pathway. Understanding mechanisms underlying mitochondrial dysfunction in cerebellar ataxia is important for the development of novel therapeutic approaches for this and other neurodegenerative diseases with secondary mitochondrial involvement.Disclosure: Dr. Garcia-Diaz has nothing to disclose. Dr. Barca has nothing to disclose. Dr. Balreira has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Tadesse has nothing to disclose. Dr. Krishna has nothing to disclose. Dr. Naini has nothing to disclose. Dr. Mariotti has nothing to disclose. Dr. Castellotti has nothing to disclose. Dr. Quinzii Hirano has nothing to disclose.Tuesday, April 19 2016, 1:00 pm-3:00 pm