Beatriz Garcia-Diaz PT -期刊文章盟盟-埃巴萨盟-安德里亚Balreira盟-路易斯·洛佩兹AU -萨巴特盟别克里希纳AU -阿里Naini盟Caterina Mariotti AU -芭芭拉Castellotti盟卡塔琳娜州Quinzii Hirano TI -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) DP - 2016年4月05 TA -神经病学PG - S30.004 VI - 86 IP - 16补充4099 - //www.ez-admanager.com/content/86/16_Supplement/S30.004.short 4100 - //www.ez-admanager.com/content/86/16_Supp首页lement/S30.004.full所以Neurology2016 4月05;86 AB -目标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,由APTX突变引起的,而编码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。 The biochemical and molecular abnormalities observed in APTX mutant and depleted cells are recapitulated by knockdown of APE1, and, importantly, are rescued by overexpression of NRF1/2 and pharmacological up-regulation of NRF2 by rosiglitazone. 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