摘要
As the population ages, age-related neurodegenerative diseases have become a major challenge in health science. Currently, the pathology of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, is still not fully understood. Remarkably, emerging evidence indicates a role of genomic DNA damage and repair in various neurodegenerative disorders. Here, we summarized the current understanding of the function of DNA damage repair, especially base excision repair and double strand break repair pathways, in a variety of neurodegenerative diseases. We concluded that exacerbation of DNA lesions is found in almost all types of neurodegenerative diseases, whereas the activities of different DNA repair pathways demonstrate distinct trends, depending on disease type and even brain region. Specifically, key enzymes involved in base excision repair are likely impaired in Alzheimer's disease and amyotrophic lateral sclerosis but activated in Parkinson's disease, while nonhomologous end joining is likely downregulated in most types of neurodegenerative diseases. Hence, impairment of nonhomologous end joining is likely a common etiology for most neurodegenerative diseases, while defects in base excision repair are likely involved in the pathology of Alzheimer's disease and amyotrophic lateral sclerosis but are Parkinson's disease, based on current findings. Although there are still discrepancies and further studies are required to completely elucidate the exact roles of DNA repair in neurodegeneration, the current studies summarized here provide crucial insights into the pathology of neurodegenerative diseases and may reveal novel drug targets for corresponding neurodegenerative diseases.
摘要译文
随着人口年龄的增长，与年龄相关的神经退行性疾病已成为健康科学中的主要挑战。目前，仍然尚未完全了解神经退行性疾病的病理，例如阿尔茨海默氏病，帕金森氏病，肌萎缩性侧面硬化症和亨廷顿氏病的病理。值得注意的是，新兴的证据表明基因组DNA损伤和修复在各种神经退行性疾病中的作用。在这里，我们总结了当前对DNA损伤修复功能的理解，尤其是碱性切除修复和双链破裂修复途径，在各种神经退行性疾病中。我们得出的结论是，在几乎所有类型的神经退行性疾病中发现了DNA病变的加剧，而不同DNA修复途径的活性取决于疾病类型，甚至大脑区域。具体而言，在阿尔茨海默氏病和肌萎缩性侧索硬化症中可能会损害参与碱基切除修复的关键酶，但在帕金森氏病中被激活，而在大多数类型的神经退行性疾病中，非同源端的结合可能会下调。因此，非同源末端连接的损伤可能是大多数神经退行性疾病的常见病因，而基础切除修复中的缺陷可能与阿尔茨海默氏病和肌萎缩性侧面硬化症的病理有关，但根据目前的发现，帕克森病是帕金森氏病。尽管仍然存在差异，并且需要进一步的研究来完全阐明DNA修复在神经变性中的确切作用，但此处概述的当前研究为神经退行性疾病的病理提供了关键的见解，并可能揭示了相应神经退行性疾病的新型药物靶标。
Nan Qin; Anke Geng;Renhao Xue*Author information Article notes Copyright;License information Disclaimer. Activated or Impaired: An Overview of DNA Repair in Neurodegenerative Diseases[J]. Aging and Disease, 2022,13(4)