title: Base excision repair in the mammalian brain: implication for age related neurodegeneration.
abstract: The repair of damaged DNA is essential to maintain longevity of an organism. The brain is a matrix of different neural cell types including proliferative astrocytes and post-mitotic neurons. Post-mitotic DNA repair is a version of proliferative DNA repair, with a reduced number of available pathways and most of these attenuated. Base excision repair (BER) is one pathway that remains robust in neurons; it is this pathway that resolves the damage due to oxidative stress. This oxidative damage is an unavoidable byproduct of respiration, and considering the high metabolic activity of neurons this type of damage is particularly pertinent in the brain. The accumulation of oxidative DNA damage over time is a central aspect of the theory of aging and repair of such chronic damage is of the highest importance. We review research conducted in BER mouse models to clarify the role of this pathway in the neural system. The requirement for BER in proliferating cells also correlates with high levels of many of the BER enzymes in neurogenesis after DNA damage. However, the pathway is also necessary for normal neural maintenance as larger infarct volumes after ischemic stroke are seen in some glycosylase deficient animals. Further, the requirement for DNA polymerase β in post-mitotic BER is potentially more important than in proliferating cells due to reduced levels of replicative polymerases. The BER response may have particular relevance for the onset and progression of many neurodegenerative diseases associated with an increase in oxidative stress including Alzheimer's.
authors: Laboratory of Molecular Gerontology, National Institute on Aging Intramural Research Program, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, United States.
authors: Peter
authors: P
authors: Sykora
authors: David M
authors: DM
authors: Wilson
authors: Vilhelm A
authors: VA
authors: Bohr
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D004195:Disease Models, Animal; D051379:Mice; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000473:pathology
keywords: Aging; BER; DNA repair; Neurodegeneration
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