DNA Damage Repair in Huntington ’s Disease and Other Neurodegenerative Diseases

AbstractRecent genome-wide association studies of Huntington ’s disease (HD) primarily highlighted genes involved in DNA damage repair mechanisms as modifiers of age at onset and disease severity, consistent with evidence that more DNA repair genes are being implicated in late age–onset neurodegenerative diseases. This provides an exciting opportunity to advance therapeutic development in HD, as these pathways have already been under intense investigation in cancer research. Also emerging are the roles of other polyglutamine disease proteins in DNA damage repair mechanisms. A potential universal trigger of oxidative DNA damage shared in these late a ge–onset diseases is the increase of reactive oxygen species (ROS) in human aging, defining an age-related mechanism that has defied other hypotheses of neurodegeneration. We discuss the potential commonality of DNA damage repair pathways in HD and other neurodegenerative diseases. Potential targe ts for therapy that may prove beneficial across many of these diseases are also identified, defining nodes in the ataxia telangiectasia-mutated (ATM) complex, mismatch repair, and poly ADP-ribose polymerases (PARPs).

Source: Neurotherapeutics - July 29, 2019 Category: Neurology Source Type: research