Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Mutagenesis. 2020 Feb 13;35(1):79-106. doi: 10.1093/mutage/gez035.
Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.
在过去的二十年中，已经进行了广泛的研究来阐明神经精神疾病的分子病因和病理生理学。在大多数神经精神疾病中，包括阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）、双相情感障碍（BD）、精神分裂症和重度抑郁症，都发现氧化应激和硝化应激增加。这种应激已知会导致生物分子（包括 DNA）发生氧化损伤。因此，在患有这些疾病的患者中观察到线粒体和核 DNA 以及 RNA 损伤增加。然而，最近的发现表明，患者的 DNA 修复途径受损，这可能表明这些 DNA 损伤也可能是其修复不足的结果。在当前的系统、批判性综述中，我们旨在使用现有文献总结核和线粒体 DNA 损伤和修复以及 RNA 损伤在神经精神疾病发病机制中的作用，即 AD、PD、ALS、BD、精神分裂症和重度抑郁症，以及讨论因素作为诊断标志物和新疗法靶点的有用性。此外，我们还强调了未来研究应该朝着阐明这些现象的新方向发展。
