Title:Impaired DNA Damage Repair as a Common Feature of Neurodegenerative Diseases and Psychiatric Disorders
Volume: 15
Issue: 2
Author(s): H. Shiwaku and H. Okazawa
Affiliation:
Keywords:
Alzheimer’s disease, DNA damage, Huntington’s disease, microcephaly, schizophrenia.
Abstract: 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.
