The role of oxidative stress in Huntington’s disease: Are antioxidants good therapeutic candidates?
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.
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Oxidative DNA damage and mitochondrial dysfunction are thought to contribute to neurodegeneration of AD, vascular dementia, HD, PD and epilepsy.
“Oxidative DNA damage and mitochondrial dysfunction are thought to contribute to the neurodegeneration of AD [75,76], vascular dementia [77], HD [78], PD [79] and epilepsy [80].”
From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [78]
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Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?
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- Authors
- Gil-Mohapel, J., Brocardo, P., & Christie, B.
- Affiliations
- University of Victoria (CA)
- ORCID
- Christie, Brian
- Venue
- Current Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2014-03-31
- Volume
- 15
- Issue
- 4
- Pages
- 454-468
- ISSN
- 1389-4501 (ISSN-L)
- OpenAlex
- W2048039256
- Cited by
- 101
- References
- 16
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 1 · 2022: 11 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 12 · 2017: 14 · 2016: 3 · 2015: 11
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Huntington's disease, oxidative stress, reactive oxygen species, antioxidants, neurodegeneration, mitochondrial dysfunction, huntingtin, CAG repeat expansion, neuronal cell death, striatum, essential fatty acids, coenzyme Q10, creatine, neuroprotective therapy
- MeSH terms
- Animals, Antioxidants, Clinical Trials as Topic, Creatine, Fatty Acids, Essential, Humans, Huntington Disease, Ubiquinone, Cell Death, Reactive Oxygen Species, Oxidative Stress
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