Department of Neurology, Duke University School of Medicine, Durham, NC, USA.
J Neurosci Res. 2021 Jan;99(1):180-189. doi: 10.1002/jnr.24592. Epub 2020 Feb 12.
Parkinson's disease (PD) is the most common movement neurodegenerative disorder. Although our understanding of the underlying mechanisms of pathogenesis in PD has greatly expanded, this knowledge thus far has failed to translate into disease-modifying therapies. Therefore, it is of the utmost urgency to interrogate further the multifactorial etiology of PD. DNA repair defects cause many neurodegenerative diseases. An exciting new PD research avenue is the role that DNA damage and repair may play in neuronal death. The goal of this mini-review was to discuss the evidence for the types of DNA damage that accumulates in PD, which has provided clues for which DNA repair pathways, such as DNA double-strand break repair, are dysfunctional. We further highlight compelling data for activation of the DNA damage response in familial and idiopathic PD. The significance of DNA damage and repair is emerging in the PD field and linking these insights to PD pathogenesis may provide new insights into PD pathophysiology and consequently lead to new therapies.
帕金森病（PD）是最常见的运动神经退行性疾病。尽管我们对 PD 发病机制的基础机制的理解有了很大的扩展，但到目前为止，这些知识还没有转化为能够改变疾病进程的治疗方法。因此，深入探究 PD 的多因素病因迫在眉睫。DNA 修复缺陷会导致许多神经退行性疾病。一个令人兴奋的新的 PD 研究方向是 DNA 损伤和修复在神经元死亡中可能发挥的作用。本综述的目的是讨论在 PD 中积累的 DNA 损伤类型的证据，这些证据为哪些 DNA 修复途径（如 DNA 双链断裂修复）出现功能障碍提供了线索。我们进一步强调了家族性和特发性 PD 中 DNA 损伤反应激活的令人信服的数据。DNA 损伤和修复的意义在 PD 领域逐渐显现，将这些见解与 PD 发病机制联系起来，可能为 PD 病理生理学提供新的见解，并最终导致新的治疗方法。
