Related Experiment Videos
Bioenergetics in Huntington's disease
1Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York 10021, USA.
Insights
Huntington's disease (HD) is an inherited neurodegenerative disorder linked to a CAG triplet repeat expansion. This review explores oxidative stress, excitotoxicity, and mitochondrial dysfunction in HD pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder.
- HD is characterized by a CAG triplet repeat expansion in the huntingtin gene on chromosome 4.
- The length of the polyglutamine tract correlates with disease onset and severity.
Purpose of the Study:
- To review current concepts on the pathogenesis of Huntington's disease.
- To discuss the involvement of oxidative stress, excitotoxicity, and mitochondrial dysfunction in HD.
Main Methods:
- Literature review and synthesis of current research on Huntington's disease.
- Discussion of proposed mechanisms of neurodegeneration in HD.
Main Results:
- Mutant huntingtin induces neuronal cell death via apoptosis.
- Disturbances in cellular energy homeostasis and oxidative damage contribute to neurodegeneration.
- Free radical-induced oxidative stress, glutamate excitotoxicity, and mitochondrial respiratory chain defects are implicated in HD pathogenesis.
Conclusions:
- Oxidative stress, excitotoxicity, and mitochondrial dysfunction are key contributors to neurodegeneration in Huntington's disease.
- Understanding these mechanisms is crucial for developing therapeutic strategies for HD.
Abstract:
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder with relentless course and prototypical clinical symptoms. In 1993 HD was associated with an expanded CAG triplet repeat stretch on chromosome 4 in the coding region of its target protein, huntington. The length of the resulting polyglutamine++ extensions correlates with lower age of onset and a higher density of ubiquitin-positive neuronal intranuclear inclusions. Recently it has been proposed that mutant huntington induces progressive neuronal cell death by an apoptotic mechanism. There is strong evidence that disturbances in cellular energy homeostasis and oxidative damage contribute to neurodegeneration. This review will summarize and discuss the current concepts that point towards an involvement of free radical-induced oxidative stress, glutamate excitotoxicity and mitochondrial respiratory chain defects in pathogenesis of HD.