Peptide SS-31 upregulates frataxin expression and improves the quality of mitochondria: implications in the treatment of Friedreich ataxia.
Peptide SS-31 upregulates frataxin expression and improves the quality of mitochondria: implications in the treatment of Friedreich ataxia.
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肽 SS-31 上调 frataxin 表达并改善线粒体质量：对弗里德赖希共济失调治疗的影响
DOI：
10.1038/s41598-017-10320-2
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发表时间：
2017-08-29
影响因子：
4.6
通讯作者：
Li K
中科院分区：
文献类型：
--
作者：
Zhao H;Li H;Hao S;Chen J;Wu J;Song C;Zhang M;Qiao T;Li K
弗里德赖希共济失调是一种进行性神经退行性疾病，由编码共济失调蛋白的FXN基因第一内含子内GAA三核苷酸重复序列扩增引起。该疾病的病理生理学被认为是由于共济失调蛋白缺乏导致的Fe-S簇生物合成的减少。目前尚无有效的治疗方法。在我们的研究中，我们证明了用靶向肽SS-31治疗减少了来自患者的淋巴母细胞和成纤维细胞中共济失调蛋白缺乏诱导的氧化应激。有趣的是，SS-31处理以剂量依赖性方式抑制性上调共济失调蛋白的蛋白水平。此外，SS-31处理增加了铁硫酶的酶活性，包括乌头酸酶和呼吸链的复合物II和III。线粒体质量的进一步评价表明，线粒体膜电位，ATP含量，NAD+/NADH和线粒体的形态都有所改善。我们的研究结果表明SS-31可能是一种早期治疗弗里德赖希共济失调的新药。
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of theFXNgene, 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.
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影响因子：
9.7
作者：
Dai, Dao-Fu;Hsieh, Edward J.;Rabinovitch, Peter S.
通讯作者：
Rabinovitch, Peter S.
DOI：
10.1073/pnas.96.20.11492
发表时间：
1999-09-28
影响因子：
11.1
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影响因子：
3.5
作者：
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影响因子：
168.9
作者：
Libri, Vincenzo;Yandim, Cihangir;Festenstein, Richard
通讯作者：
Festenstein, Richard