ArticleAmerican journal of physiology. Endocrinology and metabolism2011
Molecular characterization of skeletal muscle atrophy in the R6/2 mouse model of Huntington's disease.
Article in American journal of physiology. Endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Therapeutic strategies for Huntington's disease: current approaches and future direction.Neurodegenerative disease management · 2026Review
- Integrated effects of altered action potentials and calcium release on skeletal muscle force generation in transgenic Huntington's disease mice.Pflugers Archiv : European journal of physiology · 2026Article
- Morphological and functional phenotyping of skeletal muscle and bone in the zQ175 knock-in mouse model of Huntington's disease.Journal of Huntington's disease · 2026Article
- Metabolism in Huntington's disease: a major contributor to pathology.Metabolic brain disease · 2022Review
- Review
- Hypothalamic expression of huntingtin causes distinct metabolic changes in Huntington's disease mice.Molecular metabolism · 2022Article
- Acetylcholine receptor subunit expression in Huntington's disease mouse muscle.Biochemistry and biophysics reports · 2021Article
- Huntington's disease skeletal muscle has altered T-tubules.The Journal of general physiology · 2021Article
- CInternational journal of molecular sciences · 2021Article
- A mouse model of Huntington's disease shows altered ultrastructure of transverse tubules in skeletal muscle fibers.The Journal of general physiology · 2021Article
- Molecular Mechanisms Underlying Muscle Wasting in Huntington's Disease.International journal of molecular sciences · 2020Review
- Unexpected cell type-dependent effects of autophagy on polyglutamine aggregation revealed by natural genetic variation in C. elegans.BMC biology · 2020Article
- The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice.Free radical biology & medicine · 2020Article
- The Expanding Clinical Universe of Polyglutamine Disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2019Review
- Deterioration of mitochondrial bioenergetics and ultrastructure impairment in skeletal muscle of a transgenic minipig model in the early stages of Huntington's disease.Disease models & mechanisms · 2019Article
- Normalizing glucocorticoid levels attenuates metabolic and neuropathological symptoms in the R6/2 mouse model of huntington's disease.Neurobiology of disease · 2019Article
- Dual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington's Disease.Scientific reports · 2018Article
- Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington's Disease.Cell reports · 2018Article
- Potassium channel dysfunction in neurons and astrocytes in Huntington's disease.CNS neuroscience & therapeutics · 2018Review
- Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington's disease mice.Scientific reports · 2017Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Huntington's disease (HD), a neurodegenerative disorder caused by mutant huntingtin, is characterized by a catabolic phenotype. To determine the mechanisms underlying muscle wasting, we examined key signal transduction pathways governing muscle protein metabolism, apoptosis, and autophagy in R6/2 mice, a well-characterized transgenic model of HD. R6/2 mice exhibited increased adiposity, elevated energy expenditure, and decreased body weight and lean mass without altered food intake. Severe skeletal muscle wasting accounted for a majority of the weight loss. Protein synthesis was unexpectedly increased 19% in gastrocnemius muscle, which was associated with overactivation of basal and refeeding-stimulated mammalian target of rapamycin (mTOR) signaling, elevated Akt expression and Ser(473) phosphorylation, and decreased AMPK Thr(172) phosphorylation. Moreover, mRNA abundance of atrogenes muscle ring finger-1 and atrophy F-box, was markedly attenuated during fasting and refeeding, and the urinary excretion of 3-methylhistidine was decreased, arguing against a role for the ubiquitin proteasome-mediated proteolysis in the atrophy. In contrast, mRNA expression of several caspase genes and genes involved in the extrinsic or intrinsic apoptotic pathway, caspase-3/7, -8, and -9 activity, protein abundance of caspase-3 and -9, Fas, and Fadd, and cytochrome c release were elevated. Protein expressions of LC3B-I and -II, beclin-I, and atg5 and -7 in muscle were upregulated. Thus, mutant huntingtin in skeletal muscle results in increased protein synthesis and mTOR signaling, which is countered by activation of the apoptotic and autophagic pathways, contributing to an overall catabolic phenotype and the severe muscle wasting.
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