Mutations in DNA repair enzymes can cause two neurological clinical manifestations: a developmental impairment and a degenerative disease. Polynucleotide kinase 3′-phosphatase (PNKP) is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems. Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum. Besides, mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration. Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system. As models, we analyze PNKP-related disorders, focusing on Charcot-Marie-Tooth disease and ataxia. A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.

中文翻译：

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神经发病机制中的 DNA 修复缺陷：当所有道路都通线粒体时

DNA 修复酶的突变可导致两种神经临床表现：发育障碍和退行性疾病。多核苷酸激酶 3'-磷酸酶 (PNKP) 是一种积极参与单链和双链断裂修复系统 DNA 修复的酶。这种蛋白质或同一途径中其他蛋白质的突变导致了一组具有广泛临床谱的复杂疾病。此外，线粒体功能障碍也被认为是大脑退化的一个标志。在这里，我们提供的证据支持线粒体功能障碍和 DNA 修复缺陷在神经系统发病机制中的共同作用。作为模型，我们分析 PNKP 相关疾病，重点关注腓骨肌萎缩症和共济失调。更好地了解这种关系的分子动力学可以改善神经系统疾病的诊断和治疗。