Get started
Work

PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy

Year: 2007
Type: preprint
Abstract: The coactivator PGC-1alpha mediates key responses of skeletal muscle to motor nerve activity. We show here that neuregulin-stimulated phosphorylation of PGC-1alpha and GA-binding protein (GABP) allows recruitment of PGC-1alpha to the GABP complex and enhances transcription of a broad neuromuscular junction gene program. Since a subset of genes controlled by PGC-1alpha and GABP is dysregulated in Duchenne muscular dystrophy (DMD), we examined the effects of transgenic PGC-1alpha in muscle of mdx mice. These animals show improvement in parameters characteristic of DMD, including muscle histology, running performance, and plasma creatine kinase levels. Thus, control of PGC-1alpha levels in skeletal muscle could represent a novel avenue to prevent or treat DMD.
DOI: 10.1101/gad.1525107
Authors: Christoph Handschin, Yvonne M. Kobayashi, Sherry Chin, Patrick Seale, Kevin P. Campbell, Bruce M. Spiegelman
Language: English
Open Access status: hybrid
Funders: National Science Foundation, Muscular Dystrophy Association, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universität Zürich, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G150446594, PGC-1 and Nuclear Receptors in Adaptive Thermogenesis, Molecular mechanisms regulating skeletal muscle plasticity, PGC1 proteins, meteorin-like and energy homeostasis, PGC1alpha and Irisin in the Control of Diabetes and Obesity, G9000034354
OpenAlex ID: W6968780977
Cites: 53
Cited by: 367
Related to: 10