Impaired DNA damage repair as a common feature of neurodegenerative diseases and psychiatric disorders.
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.
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Shiwaku
Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. okazawa.npat@mri.tmd.ac.jp.
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Okazawa
D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008831:Microcephaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects
D014150:Antipsychotic Agents; D004247:DNA