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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 15
ISSUE: 4
DOI: 10.2174/1389450115666140115113734      Price:  $58









The Role of Oxidative Stress in Huntington’s Disease: Are Antioxidants Good Therapeutic Candidates?

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Author(s): Joana Gil-Mohapel, Patricia S. Brocardo and Brian R. Christie
Pages 454-468 (15)
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.
Affiliation:
Division of Medical Sciences, Island Medical Program, University of Victoria, Victoria, BC, V8W 2Y2, Canada.