Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Biomolecules. 2020 May 1;10(5):702. doi: 10.3390/biom10050702.
DNA repeat expansion disorders are a group of neuromuscular and neurodegenerative diseases that arise from the inheritance of long tracts of nucleotide repetitions, located in the regulatory region, introns, or inside the coding sequence of a gene. Although loss of protein expression and/or the gain of function of its transcribed mRNA or translated product represent the major pathogenic effect of these pathologies, mitochondrial dysfunction and imbalance in redox homeostasis are reported as common features in these disorders, deeply affecting their severity and progression. In this review, we examine the role that the redox imbalance plays in the pathological mechanisms of DNA expansion disorders and the recent advances on antioxidant treatments, particularly focusing on the expression and the activity of the transcription factor NRF2, the main cellular regulator of the antioxidant response.
DNA 重复扩展障碍是一组神经肌肉和神经退行性疾病，由核苷酸重复长链的遗传引起，位于基因的调控区域、内含子或编码序列内。尽管这些病理学的主要致病效应是蛋白质表达的丧失和/或其转录 mRNA 或翻译产物的功能获得，但线粒体功能障碍和氧化还原平衡失衡被报道为这些疾病的共同特征，这对其严重程度和进展有深远影响。在这篇综述中，我们研究了氧化还原失衡在 DNA 扩展障碍的病理机制中的作用，以及抗氧化治疗的最新进展，特别是集中在转录因子 NRF2 的表达和活性上，NRF2 是抗氧化反应的主要细胞调节剂。
