Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function.

Abstract:

:Accumulation of oxidative DNA damage in the human brain has been implicated in etiologies of post-traumatic and age-associated declines in neuronal function. In neurons, because of high metabolic rates and prolonged life span, exposure to free radicals is intense and risk for accumulation of damaged DNA is amplified. While data indicate that the brain is equipped to repair nuclear and mitochondrial DNA, it is unclear whether repair is executed by distinct subsets of the DNA-repair machinery. Likewise, there are no firm assessments of brain capacity for accurate DNA repair under normal and more so compromised conditions. Consequently, the scope of DNA repair in the brain and the impact of resolution of oxidative lesions on neuronal survival and function remain largely unknown. This review considers evidences for brain levels and activities of the base excision repair (BER) pathway in the context of newly available, comprehensive in situ hybridization analyses of genes encoding repair enzymes. These analyses suggest that not all subsets of BER are equally represented in the brain. Because BER is the major repair process for oxidatively damaged DNA, to what extent parsimonious BER may contribute to development of neuronal dysfunction and brain injury under compromised conditions, is discussed.

journal_name

Mech Ageing Dev

authors

Englander EW

doi

10.1016/j.mad.2008.02.001

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

475-82

issue

7-8

eissn

0047-6374

issn

1872-6216

pii

S0047-6374(08)00035-3

journal_volume

129

pub_type

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