Related Experiment Video
Updated: May 27, 2026
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Antioxidants in Huntington's disease
1Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY 10065, USA. johri.ashu@gmail.com
Insights
Huntington's disease involves neuronal degeneration due to a genetic mutation. Boosting antioxidant defenses and PGC-1α may slow Huntington's disease progression.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Huntington's disease (HD) is a neurodegenerative disorder characterized by selective neuronal loss, leading to motor, cognitive, and psychiatric impairments.
- HD stems from a cytosine-adenine-guanine (CAG) repeat expansion in the huntingtin gene, producing a mutant huntingtin protein with a toxic gain of function.
- This mutant protein triggers neuronal dysfunction and death through mechanisms including transcriptional impairment, excitotoxicity, oxidative damage, inflammation, apoptosis, and mitochondrial dysfunction.
Purpose of the Study:
- To explore the role of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in Huntington's disease pathogenesis.
- To investigate the contribution of oxidative damage to Huntington's disease progression.
- To identify potential therapeutic strategies targeting oxidative stress and PGC-1α pathways for Huntington's disease.
Main Methods:
- Review of existing literature on Huntington's disease mechanisms, focusing on PGC-1α and oxidative stress.
- Analysis of the implications of impaired PGC-1α expression and function in HD.
- Examination of the role of oxidative damage to lipids, proteins, and DNA in HD pathogenesis.
Main Results:
- Impaired PGC-1α expression and function are implicated in Huntington's disease, increasing vulnerability to oxidative stress and striatal degeneration.
- Significant oxidative damage to cellular components, including DNA, is a recognized feature of HD, potentially contributing to CAG repeat expansion.
- Elevated oxidized DNA bases in patient plasma may serve as a biomarker for disease progression.
Conclusions:
- Restoring PGC-1α function and enhancing antioxidant enzyme expression are promising therapeutic avenues for slowing Huntington's disease progression.
- Modulating the Nrf-2/ARE pathway or increasing PGC-1α expression could represent effective strategies for treating Huntington's disease.
- Antioxidant treatments have shown efficacy in preclinical models and hold promise for human clinical trials in Huntington's disease.
Abstract:
Huntington's disease (HD) is a prototypical neurodegenerative disease in which there is selective neuronal degeneration, which leads to progressive disability, manifesting itself as a movement disorder, with both psychiatric and cognitive impairment. The disease is caused by a cytosine-adenine-guanine (CAG) repeat expansion in the huntingtin gene, which causes an expanded polyglutamine repeat in the huntingtin protein, resulting in a protein with a novel gain of function. The mutant huntingtin protein causes neuronal dysfunction and eventual cell death in which transcriptional impairment, excitotoxicity, oxidative damage, inflammation, apoptosis and mitochondrial dysfunction are all implicated. A critical transcriptional impairment may be impaired expression and function of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a master co-regulator of mitochondrial biogenesis and expression of antioxidant enzymes. A deficiency of PGC-1α leads to increased vulnerability to oxidative stress and to striatal degeneration. The extent and severity of the oxidative damage in HD are features well recognized but perhaps under-appreciated. Oxidative damage occurs to lipids, proteins and deoxyribonucleic acid (DNA), and it has been suggested that the latter may contribute to CAG repeat expansion during DNA repair [1]. A marked elevation of oxidized DNA bases occurs in patients' plasma, which may provide a biomarker of disease progression. Antioxidants are effective in slowing disease progression in transgenic mouse models of HD, and show promise in human clinical trials. Strategies to transcriptionally increase expression of antioxidant enzymes by modulating the Nrf-2/ARE pathway, or by increasing expression of PGC-1α hold great promise for developing new treatments to slow or halt the progression of HD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
More Related Videos
Related Concept Videos
01:21Huntington Disease l: Introduction
01:24Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of its...
01:20Radical Autoxidation
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
01:24Parkinson Disease ll: Pathophysiology
01:22Alzheimer's Disease: Treatment