Molecular basis for treatment of mitochondrial myopathies
Molecular basis for treatment of mitochondrial myopathies
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DOI：
10.1007/s100720070002
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发表时间：
2000-01-01
影响因子：
3.3
通讯作者：
Turnbull, DM
中科院分区：
文献类型：
--
作者：
Taylor, RW;Wardell, TM;Turnbull, DM
线粒体DNA （mtDNA）是细胞核外唯一自主复制的DNA来源。线粒体基因组编码线粒体呼吸链的13种必需多肽。线粒体基因组缺陷可引起严重的神经系统和多系统疾病。在许多患者中，同一细胞中存在突变型和野生型mtDNA的混合物（这种情况称为异质性）。在这些患者中，突变型与野生型mtDNA的比例是至关重要的，生化缺陷仅发生在单个细胞中相对较高水平的突变mtDNA。这个阈值似乎在mtDNA疾病的发展中也至关重要。由于遗传缺陷导致氧化代谢终末阶段的功能障碍，因此药物干预的可能性很小。必须开发分子技术来逆转突变型和野生型mtDNA的比例。在本文中，我们总结了我们的方法使用抗基因组肽核酸和细胞坏死。
Mitochondrial DNA (mtDNA) is the only autonomously replicating source of DNA outside the nucleus. The mitochondrial genome encodes thirteen essential polypeptides of the mitochondrial respiratory chain. Defects of the mitochondrial genome can cause severe neurological and multi-systemic disorders. In many patients there is a mixture of mutated and wild-type mtDNA in the same cell (a situation termed heteroplasmy). In these patients the ratio of mutated to wild-type mtDNA is crucial and a biochemical defect only occurs with relatively high levels of mutated mtDNA within an individual cell. This threshold also seems to be critical in the development of mtDNA disease. Since the genetic defect causes a dysfunction in the terminal stage of oxidative metabolism, there is little potential for pharmacological intervention. Molecular techniques must be developed to reverse the ratio of mutated and wild-type mtDNA. In this paper we summarise our approach using both antigenomic peptide nucleic acids and cell necrosis.