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
-
Antithrombotic Therapy in Cardiac Embolism
Current Cardiology Reviews Editorial: Recent Advances of Cell and Gene Therapy in Kidney Diseases
Current Gene Therapy Advances in Drug Safety
Current Pharmaceutical Design A Review of Agents Patented for their Neuroprotective Properties
Recent Patents on CNS Drug Discovery (Discontinued) Role of Heat Shock Proteins in Atherosclerosis and Atrial Fibrillation
Current Immunology Reviews (Discontinued) Concepts of Egr-1 Activation – A Hub for Signal Transduction Cascades
Current Signal Transduction Therapy Actions of Relaxin on Non-Reproductive Tissues
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Danshen (Salvia miltiorrhiza Bunge): A Prospective Healing Sage for Cardiovascular Diseases
Current Pharmaceutical Design Roles of Arterial Baroreceptor Reflex During Bezold-Jarisch Reflex
Current Cardiology Reviews New Challenges and Strategies for Cardiac Disease: Autophagy, mTOR, and AMP-activated Protein Kinase
Current Neurovascular Research Tumor Necrosis Factor-α-Mediated Pulmonary Endothelial Barrier Dysfunction
Current Respiratory Medicine Reviews Mesenchymal Stem Cells Targeting of Systemic Disorders in Age-related Macular Degeneration
Current Tissue Engineering (Discontinued) Efficacy of Zofenopril Alone or in Combination with Hydrochlorothiazide in Patients with Kidney Dysfunction
Current Clinical Pharmacology Vascular Endothelium and Hypovolemic Shock
Current Vascular Pharmacology Thymoquinone Anticancer Discovery: Possible Mechanisms
Current Drug Discovery Technologies Diverse Functions and Mechanisms of Pericytes in Ischemic Stroke
Current Neuropharmacology Chemoprevention of Colorectal Carcinogenesis by Natural Anti-Inflammatory Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry A Facile “Click Chemistry” Approach to Novel Flavonol Glycoconjugates and Their Cytotoxic Activity
Letters in Organic Chemistry Sesamin and Sesamolin: Natures Therapeutic Lignans
Current Enzyme Inhibition Current Strategies to Minimize Ischemia-Reperfusion Injury in Liver Transplantation: A Systematic Review
Reviews on Recent Clinical Trials