DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives?

Abstract

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.