Abstract
Huntington’s disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.
Keywords: Antioxidant, clinical trial, Huntington’s disease, oxidative stress, reactive oxygen species, transgenic mice.
Current Drug Targets
Title:The Role of Oxidative Stress in Huntington’s Disease: Are Antioxidants Good Therapeutic Candidates?
Volume: 15 Issue: 4
Author(s): Joana Gil-Mohapel, Patricia S. Brocardo and Brian R. Christie
Affiliation:
Keywords: Antioxidant, clinical trial, Huntington’s disease, oxidative stress, reactive oxygen species, transgenic mice.
Abstract: Huntington’s disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.
Export Options
About this article
Cite this article as:
Gil-Mohapel Joana, Brocardo S. Patricia and Christie R. Brian, The Role of Oxidative Stress in Huntington’s Disease: Are Antioxidants Good Therapeutic Candidates?, Current Drug Targets 2014; 15 (4) . https://dx.doi.org/10.2174/1389450115666140115113734
DOI https://dx.doi.org/10.2174/1389450115666140115113734 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
Related Articles
-
Discovery of Nesfatin-1 and Overview of Biological Actions and New Developments
Current Pharmaceutical Design Structure-Function Relationships of PEDF
Current Molecular Medicine Current Research on Opioid Receptor Function
Current Drug Targets Cardiovascular Magnetic Resonance Imaging: State of the Art
Current Cardiology Reviews On the Involvement of Mitochondrial Intermembrane Junctional Complexes in Apoptosis
Current Medicinal Chemistry Plasminogen Activation-Based Thrombolysis for Ischaemic Stroke: The Diversity of Targets may Demand New Approaches
Current Drug Targets Functional Biomolecule Delivery Systems and Bioengineering in Cartilage Regeneration
Current Pharmaceutical Biotechnology Adult Stem Cell Therapy for Cardiac Repair in Patients After Acute Myocardial Infarction Leading to Ischemic Heart Failure: An Overview of Evidence from the Recent Clinical Trials
Current Cardiology Reviews The p38α Kinase Plays a Central Role In Inflammation
Current Topics in Medicinal Chemistry The Changing Landscape of Voltage-Gated Calcium Channels in Neurovascular Disorders and in Neurodegenerative Diseases
Current Neuropharmacology Melatonin and Synthetic Melatoninergic Agonists in Psychiatric and Age-associated Disorders: Successful and Unsuccessful Approaches
Current Pharmaceutical Design Serpinins: Role in Granule Biogenesis, Inhibition of Cell Death and Cardiac Function
Current Medicinal Chemistry Abstracts from Speakers
Cardiovascular & Hematological Disorders-Drug Targets Low Lymphocyte Count and Cardiovascular Diseases
Current Medicinal Chemistry In Vitro Modeling of the Blood-Brain Barrier: Simplicity Versus Complexity
Current Pharmaceutical Design Neuroprotective Effects of Ellagitannins: A Brief Review
Current Drug Targets Preclinical Safety and Pharmacokinetic Profile of 3K3A-APC, a Novel, Modified Activated Protein C for Ischemic Stroke
Current Pharmaceutical Design Is the Deficiency of Vitamin B12 Related to Oxidative Stress and Neurotoxicity in Parkinsons Patients?
CNS & Neurological Disorders - Drug Targets Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review
Current Medicinal Chemistry Indian Spices for Healthy Heart - An Overview
Current Cardiology Reviews