Back to Search
Start Over
Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Jul 26; Vol. 22 (15). Date of Electronic Publication: 2021 Jul 26. - Publication Year :
- 2021
-
Abstract
- Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways. However, the underlying therapeutic mechanisms of GH or IGF-1 in SCA3 are not fully understood. In the present study, tissue-specific genome-scale metabolic network models for SCA3 transgenic mice were proposed based on RNA-seq. An integrative transcriptomic and metabolic network analysis of a SCA3 transgenic mouse model revealed that metabolic signaling pathways were activated to compensate for the metabolic remodeling caused by SCA3 genetic modifications. The effect of IGF-1 intervention on the pathology and balance of SCA3 disease was also explored. IGF-1 has been shown to invoke signaling pathways and improve mitochondrial function and glycolysis pathways to restore cellular functions. As one of the downregulated factors in SCA3 transgenic mice, IGF-1 could be a potential biomarker and therapeutic target.
- Subjects :
- Animals
Ataxin-3 genetics
Ataxin-3 metabolism
Growth Hormone genetics
Growth Hormone metabolism
Insulin-Like Growth Factor I genetics
Machado-Joseph Disease genetics
Mice
Mice, Transgenic
Cellular Reprogramming
Gene Expression Profiling
Insulin-Like Growth Factor I metabolism
Machado-Joseph Disease metabolism
Models, Biological
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34360740
- Full Text :
- https://doi.org/10.3390/ijms22157974