Abstract
Alzheimer’s disease (AD) is a common, progressive neurodegenerative disorder without highly effective therapies. The etiology of AD is heterogeneous with amyloid-beta plaques, neurofibrillary tangles, oxidative stress, and aberrant DNA methylation all implicated in the disease pathogenesis. DNA methylation is a well-established process for regulating gene expression and has been found to regulate a growing number of important genes involved in AD development and progression. Additionally, aberrations in one-carbon metabolism are a common finding in AD patients with individuals exhibiting low S-adenosylmethionine and high homocysteine levels as well as low folate and vitamin B. Oxidative stress is considered one of the earliest events in AD pathogenesis and is thought to contribute largely to neuronal cell death. Emerging evidence suggests an interaction exists between oxidative stress and DNA methylation; however, the mechanism(s) remain unclear. This review summarizes known and potential genes implicated in AD that are regulated by DNA methylation and oxidative stress. We also highlight the evidence for the role of oxidative damage contributing to DNA hypomethylation in AD patients through several mechanisms as well as implications for disease understanding and therapeutic development.
Keywords: Alzheimer’s disease, DNA methylation, epigenetics, oxidative stress, gene regulation, Gene expression, Aberrant epigenetic regulation, AD etiology.
Current Alzheimer Research
Title:The Role for Oxidative Stress in Aberrant DNA Methylation in Alzheimer’s Disease
Volume: 9 Issue: 9
Author(s): Jessica L. Fleming, Christopher J. Phiel and Amanda Ewart Toland
Affiliation:
Keywords: Alzheimer’s disease, DNA methylation, epigenetics, oxidative stress, gene regulation, Gene expression, Aberrant epigenetic regulation, AD etiology.
Abstract: Alzheimer’s disease (AD) is a common, progressive neurodegenerative disorder without highly effective therapies. The etiology of AD is heterogeneous with amyloid-beta plaques, neurofibrillary tangles, oxidative stress, and aberrant DNA methylation all implicated in the disease pathogenesis. DNA methylation is a well-established process for regulating gene expression and has been found to regulate a growing number of important genes involved in AD development and progression. Additionally, aberrations in one-carbon metabolism are a common finding in AD patients with individuals exhibiting low S-adenosylmethionine and high homocysteine levels as well as low folate and vitamin B. Oxidative stress is considered one of the earliest events in AD pathogenesis and is thought to contribute largely to neuronal cell death. Emerging evidence suggests an interaction exists between oxidative stress and DNA methylation; however, the mechanism(s) remain unclear. This review summarizes known and potential genes implicated in AD that are regulated by DNA methylation and oxidative stress. We also highlight the evidence for the role of oxidative damage contributing to DNA hypomethylation in AD patients through several mechanisms as well as implications for disease understanding and therapeutic development.
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Cite this article as:
L. Fleming Jessica, J. Phiel Christopher and Ewart Toland Amanda, The Role for Oxidative Stress in Aberrant DNA Methylation in Alzheimer’s Disease, Current Alzheimer Research 2012; 9 (9) . https://dx.doi.org/10.2174/156720512803569000
DOI https://dx.doi.org/10.2174/156720512803569000 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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