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Protective Effects of Antioxidants in Huntington's Disease: an Extensive Review
Musthafa Mohamed Essa1,2, Marzieh Moghadas3, Taher Ba-Omar3
1Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, Oman. drmdessa@gmail.com.
Insights
Huntington's disease (HD) involves mutated huntingtin (HTT) protein accumulation, causing neuronal oxidative stress. Antioxidants are explored for managing this neurodegenerative disease, as current treatments only address symptoms.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Huntington's disease (HD) is an inherited neurodegenerative disorder affecting the central nervous system (CNS).
- Clinical manifestations include motor, cognitive, and psychiatric impairments, often starting between ages 30-50.
- Genetic mutations in the huntingtin (HTT) gene lead to abnormal huntingtin protein (mHtt) accumulation.
Purpose of the Study:
- To review cellular changes and neuronal energy metabolism in HD.
- To explore the therapeutic potential of antioxidants in managing HD-related oxidative stress and neurodegeneration.
Main Methods:
- Literature review focusing on cellular mechanisms in HD.
- Analysis of studies investigating mitochondrial dysfunction and oxidative stress in HD.
- Examination of research on antioxidant and nutraceutical interventions for HD.
Main Results:
- Mutated huntingtin (mHtt) protein accumulation causes neuronal dysfunction and erratic movements.
- Excessive HTT gene repeats lead to reactive oxygen species (ROS) production and mitochondrial (MT) oxidative stress.
- MT dysfunction and oxidative stress are critical factors in HD neurodegeneration.
Conclusions:
- Current HD therapeutics offer only symptomatic relief; no cure or disease-modifying treatments exist.
- Antioxidant supplementation shows promise for mitigating oxidative damage and neurodegeneration in HD.
- Further research into antioxidants is crucial for developing effective HD management strategies.
Abstract:
Huntington's disease (HD) is a hereditary neurodegenerative disease of the central nervous system (CNS). Onset of HD occurs between the ages of 30 and 50 years, although few cases are reported among children and elderly. HD appears to be less common in some populations such as those of Japanese, Chinese, and African descent. Clinical features of HD include motor dysfunction (involuntary movements of the face and body, abnormalities in gait, posture and balance), cognitive impairment (obsessive-compulsive disorder), and psychiatric disorders (dementia). Mutation in either of the two copies of a gene called huntingtin (HTT), which codes genetic information for a protein called "huntingtin (Htt)", precipitates the disease in an individual. Expansion of cytosine-adenine-guanine (CAG) triplet repeats in the HTT gene results in an abnormal Htt protein. Intracellular neuronal accumulation of the mutated Htt protein (mHtt) causes distinctive erratic movements associated with HD. Further, excessive accumulation of the HTT gene repeats causes abnormal production of reactive oxygen species (ROS) and the ensuing mitochondrial (MT) oxidative stress in neurons. Since there is neither a cure nor a promising strategy to delay onset or progression of HD currently available, therapeutics are mainly focusing only on symptomatic management. Several studies have shown that MT dysfunction-mediated oxidative stress is a key factor for the neurodegeneration observed in HD. Supplementation of antioxidants and nutraceuticals has been widely studied in the management of oxidative damage, an associated complication in HD. Therefore, various antioxidants are used as therapeutics for managing and/or treating HD. The present review aimed at delving into the abnormal cellular changes and energy kinetics of the neurons expressing the mHtt gene and the therapeutic roles of antioxidants in HD.