As mitochondria are vulnerable to oxidative damage and represent the main source of reactive oxygen species (ROS), they are considered key tuners of ROS metabolism and buffering, whose dysfunction can progressively impact neuronal networks and disease. Defects in DNA repair and DNA damage response (DDR) may also affect neuronal health and lead to neuropathology. A number of congenital DNA repair and DDR defective syndromes, indeed, show neurological phenotypes, and a growing body of evidence indicate that defects in the mechanisms that control genome stability in neurons acts as aging-related modifiers of common neurodegenerative diseases such as Alzheimer, Parkinson's, Huntington diseases and Amyotrophic Lateral Sclerosis.

In this review we elaborate on the established principles and recent concepts supporting the hypothesis that deficiencies in either DNA repair or DDR might contribute to neurodegeneration via mechanisms involving mitochondrial dysfunction/deranged metabolism.

由于线粒体容易受到氧化损伤并代表活性氧 (ROS) 的主要来源，因此它们被认为是 ROS 代谢和缓冲的关键调节剂，其功能障碍会逐渐影响神经元网络和疾病。DNA 修复和 DNA 损伤反应 (DDR) 的缺陷也可能影响神经元健康并导致神经病理学。许多先天性 DNA 修复和 DDR 缺陷综合征确实显示出神经表型，越来越多的证据表明，控制神经元基因组稳定性的机制中的缺陷是常见神经退行性疾病（如阿尔茨海默氏症、帕金森氏症）的衰老相关调节剂、亨廷顿病和肌萎缩侧索硬化症。

在这篇综述中，我们详细阐述了支持以下假设的既定原则和最新概念，即 DNA 修复或 DDR 的缺陷可能通过涉及线粒体功能障碍/代谢紊乱的机制导致神经变性。