Accumulation of DNA damage and impairment of DNA repair systems are involved in the
pathogenesis of different neurodegenerative diseases. Whenever DNA damage is too extensive, the
DNA damage response pathway provides for triggering cellular senescence and/or apoptosis. However,
whether the increased level of DNA damage in neurodegenerative disorders is a cause rather than the
consequence of neurodegenerative events remains to be established. Among possible DNA lesions,
DNA double strand breaks (DSBs) are rare events, nevertheless they are the most lethal form of DNA
damage. In neurons, DSBs are particularly deleterious because of their reduced DNA repair capability
as compared to proliferating cells.
Here, we provide a description of DSB repair systems and describe human studies showing the presence
of several types of DNA lesions in three major neurodegenerative diseases including Alzheimer’s
disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Then, we analyze the role of
DSB accumulation and deficiency of DSB repair systems in neurodegeneration by examining studies
on animal models of neurodegenerative diseases.
Keywords: Alzheimer's disease, DNA damage, DNA repair, DNA double strand breaks, Huntington's disease, neurodegenerative
diseases, Parkinson's disease.
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