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


Handschin, C; Kobayashi, Y M; Chin, S; Seale, P; Campbell, K P; Spiegelman, B M (2007). PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes and Development, 21(7):770-783.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2007
Deposited On:18 Mar 2008 10:04
Last Modified:06 Dec 2017 13:45
Publisher:Cold Spring Harbor Laboratory Press
ISSN:0890-9369
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/gad.1525107
PubMed ID:17403779

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