Abstract
The efficiency of DNA damage repair declines with aging similarly to other cellular functions, and the decline is faster in neurodegenerative diseases. We suppose this is one of the molecular bases by which aging promotes neurodegeneration. Especially, neurons are vulnerable to DNA damage because they have no opportunity of cell division. We have found that the causative proteins of polyglutamine disease inhibit HGMB1/2, which regulate the architecture of DNA, and therefore DNA double strand break is increased. Additionally, we have reported that Ku70 and VCP, both of which have central functions in DNA double strand break repair, are disturbed by polyglutamine proteins. Also, neurodegenerative diseases including ataxia- telangiectasia, early- onset ataxia with ocular motor apraxia and hypoalbuminemia / ataxia with oculomotor apraxia type 1, xeroderma pigmentosum, and Cockayne syndrome are caused by mutations in DNA repair- related genes. These studies suggest that DNA damage is common pathology of various neurodegenerative diseases, and that aging, more than diseases, can be controlled by improving the repair of DNA damage.
