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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Inhibitors of Cathepsin B
Current Medicinal Chemistry The Impact of Docosahexaenoic Acid on Alzheimer’s Disease: Is There a Role of the Blood-Brain Barrier?
Current Clinical Pharmacology Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity
Anti-Cancer Agents in Medicinal Chemistry Tumor Targeting with RGD Peptide Ligands-Design of New Molecular Conjugates for Imaging and Therapy of Cancers
Anti-Cancer Agents in Medicinal Chemistry Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems
Recent Patents on Anti-Cancer Drug Discovery Active-Targeted Nanotherapy Strategies for Prostate Cancer
Current Cancer Drug Targets Structure, Gating and Basic Functions of the Ca2+-activated K Channel of Intermediate Conductance
Current Neuropharmacology P38 MAPK Contributes to Resistance and Invasiveness of HER2- Overexpressing Breast Cancer
Current Medicinal Chemistry Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis
Current Pharmaceutical Design Ion Channels and Epilepsy
Current Pharmaceutical Design Mitochondria as Possible Pharmaceutical Targets for the Effects of Vitamin E and its Homologues in Oxidative Stress-Related Diseases
Current Pharmaceutical Design Design, Synthesis and Anticancer Activity Evaluation of Diazepinomicin Derivatives
Letters in Drug Design & Discovery Anti-VEGF Mediated Immunomodulatory Role of Phytochemicals: Scientific Exposition for Plausible HCC Treatment
Current Drug Targets Medulloblastoma: Role of Developmental Pathways, DNA Repair Signaling, and Other Players
Current Molecular Medicine CPP-Based Bioactive Drug Delivery to Penetrate the Blood-Brain Barrier: A Potential Therapy for Glioblastoma Multiforme
Current Drug Targets Monofunctional Platinum (PtII) Compounds – Shifting the Paradigm in Designing New Pt-based Anticancer Agents
Current Medicinal Chemistry Targeting the Akt Kinase to Modulate Survival, Invasiveness and Drug Resistance of Cancer Cells
Current Medicinal Chemistry Microtubule Targeting Agents: A Benchmark in Cancer Therapy
Current Drug Therapy Metabolism and the Paradoxical Effects of Arsenic: Carcinogenesis and Anticancer
Current Medicinal Chemistry