Abstract
The vast majority of the studies performed so far and aimed at elucidating DNA repair mechanisms has been performed in mitotic cells, such as transformed or cancer cell lines. Therefore, our understanding of DNA repair mechanisms in post-mitotic cells, such as neurons, remains one of the most exciting areas for future investigations. Markers of DNA damage, particularly oxidative DNA damage, have been largely found in brain regions, peripheral tissues, and biological fluids of Alzheimers disease (AD) patients. Moreover, recent studies from our and other groups in individuals affected by Mild Cognitive Impairment provided evidence that oxidative DNA damage is one of the earliest detectable events within the progression from a normal brain to dementia. Almost one decade ago a decrease in the DNA base excision repair (BER) activity was observed in post mortem brain regions of AD individuals, leading to the hypothesis that the brain in AD might be subjected to the double insult of increased DNA damage, as well as deficiencies of DNA repair pathways. Subsequent studies have provided accumulating evidence of impaired DNA repair in AD. Moreover, functional variants and polymorphisms of DNA repair genes have been the focus of several cancer association studies, but only in recent years some of them have been investigated as possible AD risk factors. The few studies performed so far suggest that some variants might play a role in AD pathogenesis and deserve further investigations. Here, we summarize the current knowledge of DNA damage and repair in AD pathogenesis.
Keywords: Alzheimer's disease, DNA damage, oxidative DNA damage, DNA repair, Mild Cognitive Impairment
Current Alzheimer Research
Title: DNA Damage and Repair in Alzheimers Disease
Volume: 6 Issue: 1
Author(s): Fabio Coppede and Lucia Migliore
Affiliation:
Keywords: Alzheimer's disease, DNA damage, oxidative DNA damage, DNA repair, Mild Cognitive Impairment
Abstract: The vast majority of the studies performed so far and aimed at elucidating DNA repair mechanisms has been performed in mitotic cells, such as transformed or cancer cell lines. Therefore, our understanding of DNA repair mechanisms in post-mitotic cells, such as neurons, remains one of the most exciting areas for future investigations. Markers of DNA damage, particularly oxidative DNA damage, have been largely found in brain regions, peripheral tissues, and biological fluids of Alzheimers disease (AD) patients. Moreover, recent studies from our and other groups in individuals affected by Mild Cognitive Impairment provided evidence that oxidative DNA damage is one of the earliest detectable events within the progression from a normal brain to dementia. Almost one decade ago a decrease in the DNA base excision repair (BER) activity was observed in post mortem brain regions of AD individuals, leading to the hypothesis that the brain in AD might be subjected to the double insult of increased DNA damage, as well as deficiencies of DNA repair pathways. Subsequent studies have provided accumulating evidence of impaired DNA repair in AD. Moreover, functional variants and polymorphisms of DNA repair genes have been the focus of several cancer association studies, but only in recent years some of them have been investigated as possible AD risk factors. The few studies performed so far suggest that some variants might play a role in AD pathogenesis and deserve further investigations. Here, we summarize the current knowledge of DNA damage and repair in AD pathogenesis.
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Cite this article as:
Coppede Fabio and Migliore Lucia, DNA Damage and Repair in Alzheimers Disease, Current Alzheimer Research 2009; 6 (1) . https://dx.doi.org/10.2174/156720509787313970
DOI https://dx.doi.org/10.2174/156720509787313970 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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