Molecular Mechanisms Underlying Muscle Wasting in Huntington’s Disease
Abstract
:1. Introduction
2. Loss of Body Weight and Body Mass Index
3. Physiology of HD Skeletal Muscle
4. Morphology of HD Skeletal Muscle and Protein Aggregates
5. Does Mutant Huntingtin Affect Differentiation of Skeletal Muscle Cells?
6. Activation of Cellular Stress Response
6.1. Protein Synthesis and Degradation
6.2. Inflammation
6.3. Apoptosis
7. Mitochondrial Dysfunction in HD Skeletal Muscle
7.1. Deficits of the Energy Metabolism
7.2. Aberrations of the Mitochondrial Morphology
7.3. Impairment of the Mitochondrial Electron Transport Chain
7.4. Role of PGC1-α in the Mitochondrial Anomalies and Abnormal Distribution of Fiber Types
8. Muscle Fiber Type Transition
9. Defects of Motoneurons
10. Therapies for HD Treatment
11. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name | Type | DNA Construct | CAG Repeats Length | AGE of Onset | Mutant HTT Expression* | Reference |
---|---|---|---|---|---|---|
R6/2 mouse | Transgenic | Promoter and exon 1 of human Htt gene | 144 | 9–11 weeks (juvenile HD) | 75% | [43] |
R6/1 mouse | Transgenic | Promoter and exon 1 of human Htt gene | 116 | 4–5 months | 30% | [43] |
NLS-N171-82Q mouse | Transgenic | Mouse prion promoter and human sequence for the first 171 N-terminal amino acids of Htt | 82 | 9–11 weeks (juvenile HD) | 10–20% | [44,45,46,47] |
HdhQn mouse | Knock-in | Knock-in of variable number of CAG repeats into mouse Htt locus | 92–200 | Depending on the length of the CAG repeats | 100% | [40,41,42,48,49] |
BACHD mouse | Transgenic | Full-length human Htt gene under human Htt promoter | 97 | Slow disease progression and normal life span | 100% | [50,51] |
YACQn mouse | Transgenic | Full-length human Htt gene with variable number of CAG repeats under human Htt promoter | 48–128 | Depending on the length of the CAG repeats | 30–100% | [52,53,54,55] |
Mini pigs | Transgenic | Human promoter and human sequence for the first 548 N-terminal amino acids of Htt | 124 | Slow progression of the disease | 100% | [56] |
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Bozzi, M.; Sciandra, F. Molecular Mechanisms Underlying Muscle Wasting in Huntington’s Disease. Int. J. Mol. Sci. 2020, 21, 8314. https://doi.org/10.3390/ijms21218314
Bozzi M, Sciandra F. Molecular Mechanisms Underlying Muscle Wasting in Huntington’s Disease. International Journal of Molecular Sciences. 2020; 21(21):8314. https://doi.org/10.3390/ijms21218314
Chicago/Turabian StyleBozzi, Manuela, and Francesca Sciandra. 2020. "Molecular Mechanisms Underlying Muscle Wasting in Huntington’s Disease" International Journal of Molecular Sciences 21, no. 21: 8314. https://doi.org/10.3390/ijms21218314