Shiwaku H, Okazawa H
Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Curr Mol Med. 2015;15(2):119-28. doi: 10.2174/1566524015666150303002556.
Impaired DNA damage repair is a common pathological endophenotype of some types of neurodegenerative diseases, intellectual disabilities, and psychiatric diseases. Dysfunctional DNA repair and DNA damage, including DNA double-stranded breaks, are linked to transcriptional dysfunction and abnormal DNA methylation. Impaired DNA repair in neural stem cells leads to microcephaly or cerebellar ataxia. Furthermore, DNA repair defects and DNA damage in mature neurons lead to progressive cognitive impairment, which might be a common feature of Alzheimer's disease, Huntington's disease, and other polyglutamine diseases. Oxidative DNA damage and altered DNA repair gene expression are observed in GABAergic neurons in schizophrenia. These findings indicate that impaired DNA repair is a common pathological endophenotype of neurological diseases, and that DNA damage might lead to diverse disease symptoms dependent on timing and the affected cell type.
DNA损伤修复受损是某些类型神经退行性疾病、智力障碍和精神疾病常见的病理内表型。功能失调的DNA修复和DNA损伤，包括DNA双链断裂，与转录功能障碍和异常DNA甲基化有关。神经干细胞中DNA修复受损会导致小头畸形或小脑共济失调。此外，成熟神经元中的DNA修复缺陷和DNA损伤会导致进行性认知障碍，这可能是阿尔茨海默病、亨廷顿病和其他多聚谷氨酰胺疾病的共同特征。在精神分裂症的γ-氨基丁酸能神经元中观察到氧化性DNA损伤和DNA修复基因表达改变。这些发现表明，DNA修复受损是神经疾病常见的病理内表型，并且DNA损伤可能根据时间和受影响的细胞类型导致多种疾病症状。
