Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 210093, Nanjing, P. R. China.
Medical School of Henan Polytechnic University, 454000, Jiaozuo, P. R. China.
Sci Rep. 2017 Aug 29;7(1):9840. doi: 10.1038/s41598-017-10320-2.
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of the FXN gene, which encodes frataxin. The pathophysiology of the disease is thought to be derived from the decrease of Fe-S cluster biogenesis due to frataxin deficiency. There is currently no effective treatment for the disease. In our study, we demonstrated that treatment with the mitochondrion-targeted peptide SS-31 reduced frataxin deficiency-induced oxidative stress in lymphoblasts and fibroblasts derived from patients. Interestingly, SS-31 treatment translationally upregulated the protein level of frataxin in a dose-dependent manner. Furthermore, SS-31 treatment increased the enzymatic activities of the iron-sulphur enzymes, including aconitase and complex II and III of the respiratory chain. Further evaluation of the quality of mitochondria showed that mitochondrial membrane potential, ATP content, NAD/NADH, and the morphology of mitochondria all improved. Our results suggest that SS-31 might potentially be a new drug for the early treatment of Friedreich ataxia.
弗里德赖希共济失调是一种进行性神经退行性疾病，由 FXN 基因第一内含子内 GAA 三核苷酸重复扩增引起，该基因编码 frataxin。该疾病的病理生理学被认为源自 frataxin 缺乏导致的 Fe-S 簇生物发生减少。目前，该疾病尚无有效的治疗方法。在我们的研究中，我们证明了靶向线粒体的肽 SS-31 可减少由 frataxin 缺乏引起的患者来源的淋巴母细胞和成纤维细胞中的氧化应激。有趣的是，SS-31 以剂量依赖的方式翻译上调 frataxin 的蛋白水平。此外，SS-31 处理增加了铁硫酶的酶活性，包括 aconitase 和呼吸链的复合物 II 和 III。进一步评估线粒体的质量表明，线粒体膜电位、ATP 含量、NAD/NADH 和线粒体形态均得到改善。我们的结果表明，SS-31 可能是治疗弗里德赖希共济失调的一种新的早期治疗药物。
