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A genetic modifier suggests that endurance exercise exacerbates Huntington's disease
Silvia Corrochano1, Gonzalo Blanco2, Debbie Williams1
1Mammalian Genetics Unit, Harwell Institute, Medical Research Council, Oxfordshire, UK.
Human Molecular Genetics
|March 7, 2018
Summary
Huntington's disease (HD) research reveals skeletal muscle mutations worsen the condition. Surprisingly, endurance exercise also proved detrimental, suggesting physical activity may harm neurodegeneration.
Area of Science:
- Neuroscience
- Genetics
- Muscle Physiology
Background:
- Huntington's disease (HD) is caused by polyglutamine expansions in the huntingtin gene.
- Huntingtin protein affects multiple organs, not just the brain.
- Genetic and environmental factors modify HD onset and progression.
Purpose of the Study:
- Identify novel genetic modifiers of Huntington's disease.
- Investigate the role of skeletal muscle in HD pathogenesis.
- Determine the impact of exercise on HD progression.
Main Methods:
- Performed an unbiased mutagenesis screen in an HD mouse model.
- Generated and analyzed double mutant mice (HD; Scn4aDgn/+).
- Evaluated the effects of endurance exercise training on HD mice.
Main Results:
- A mutation in the skeletal muscle sodium channel gene (Scn4a) enhanced HD.
- HD; Scn4aDgn/+ mice exhibited reduced survival, weight loss, and muscle atrophy.
- Endurance exercise worsened HD phenotypes in mice, mimicking adaptive muscle changes.
Conclusions:
- Skeletal muscle plays a significant role in modulating Huntington's disease progression.
- Certain types of physical exercise may be harmful in neurodegenerative conditions like HD.
- This study highlights a novel link between muscle function and systemic neurodegeneration.