ArticleHuman molecular genetics2018
A genetic modifier suggests that endurance exercise exacerbates Huntington's disease.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Brain-Periphery Interactions in Huntington's Disease: Mediators and Lifestyle Interventions.International journal of molecular sciences · 2024Review
- Exercise attenuates polyglutamine-mediated neuromuscular degeneration in a mouse model of spinal and bulbar muscular atrophy.Journal of cachexia, sarcopenia and muscle · 2024Article
- Longitudinal home-cage automated assessment of climbing behavior shows sexual dimorphism and aging-related decrease in C57BL/6J healthy mice and allows early detection of motor impairment in the N171-82Q mouse model of Huntington's disease.Frontiers in behavioral neuroscience · 2023Article
- Effects of Exercise on Skeletal Muscle Pathophysiology in Huntington's Disease.Journal of functional morphology and kinesiology · 2022Review
- Endurance exercise ameliorates phenotypes ineLife · 2022Article
- Systemic manifestation and contribution of peripheral tissues to Huntington's disease pathogenesis.Ageing research reviews · 2021Review
- Physical Exercise-Induced Myokines in Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- High frequency of intermediary alleles in the HTT gene in Northern Sweden - The Swedish Huntingtin Alleles and Phenotype (SHAPE) study.Scientific reports · 2020Article
- New Synthetic 3-Benzoyl-5-Hydroxy-2Oxidative medicine and cellular longevity · 2020Article
- Impacts of exercise interventions on different diseases and organ functions in mice.Journal of sport and health science · 2020Review
- Uses for humanised mouse models in precision medicine for neurodegenerative disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Review
- Skeletal Muscle Modulates Huntington's Disease Pathogenesis in Mice: Role of Physical Exercise.Journal of experimental neuroscience · 2018Article
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16 authors at 6 institutions in 3 countries.
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Abstract
Polyglutamine expansions in the huntingtin gene cause Huntington's disease (HD). Huntingtin is ubiquitously expressed, leading to pathological alterations also in peripheral organs. Variations in the length of the polyglutamine tract explain up to 70% of the age-at-onset variance, with the rest of the variance attributed to genetic and environmental modifiers. To identify novel disease modifiers, we performed an unbiased mutagenesis screen on an HD mouse model, identifying a mutation in the skeletal muscle voltage-gated sodium channel (Scn4a, termed 'draggen' mutation) as a novel disease enhancer. Double mutant mice (HD; Scn4aDgn/+) had decreased survival, weight loss and muscle atrophy. Expression patterns show that the main tissue affected is skeletal muscle. Intriguingly, muscles from HD; Scn4aDgn/+ mice showed adaptive changes similar to those found in endurance exercise, including AMPK activation, fibre type switching and upregulation of mitochondrial biogenesis. Therefore, we evaluated the effects of endurance training on HD mice. Crucially, this training regime also led to detrimental effects on HD mice. Overall, these results reveal a novel role for skeletal muscle in modulating systemic HD pathogenesis, suggesting that some forms of physical exercise could be deleterious in neurodegeneration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.