Lin Y.-TLin Y.-SCheng W.-LChang J.-CChao Y.-CLiu C.-SAN-CHI WEI2022-04-252022-04-25202116616596https://www.scopus.com/inward/record.uri?eid=2-s2.0-85111154677&doi=10.3390%2fijms22157974&partnerID=40&md5=4fc6912c01c4e49357fe6b708c01b5f9https://scholars.lib.ntu.edu.tw/handle/123456789/606951Spinocerebellar 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. ? 2021 by the author. Licensee MDPI, Basel, Switzerland.Context-specific metabolic networksInsulin-like growth factor 1RNA-seqSpinocerebellar ataxia type 3ataxin 3Atxn3 protein, mousegrowth hormoneinsulin-like growth factor-1, mousesomatomedin Canimalbiological modelgene expression profilinggeneticsMachado Joseph diseasemetabolismmousenuclear reprogrammingsignal transductiontransgenic mouseAnimalsAtaxin-3Cellular ReprogrammingGene Expression ProfilingGrowth HormoneInsulin-Like Growth Factor IMachado-Joseph DiseaseMiceMice, TransgenicModels, BiologicalSignal Transductionjournal article10.3390/ijms22157974343607402-s2.0-85111154677