JCB logo
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 18 January 2005. doi:10.1083/jcb.200407021
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 2, 193-199
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1276K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dobrowolny, G.
Right arrow Articles by Musarò, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dobrowolny, G.
Right arrow Articles by Musarò, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Report

Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model



Gabriella Dobrowolny1, Cristina Giacinti1, Laura Pelosi1, Carmine Nicoletti1, Nadine Winn2, Laura Barberi1, Mario Molinaro1, Nadia Rosenthal2, and Antonio Musarò1,3

1 Department of Histology and Medical Embryology, CE-BEMM and Interuniversity Institute of Myology, University of Rome "La Sapienza", 14 00161 Rome, Italy
2 EMBL Mouse Biology Program, 00016 Monterotondo, Italy
3 Edith Cowan University, 6027 Western Australia

Correspondence to Antonio Musarò: antonio.musaro{at}uniroma1.it; or Nadia Rosenthal: rosenthal{at}embl-monterotondo.it


Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective degeneration of motor neurons, atrophy, and paralysis of skeletal muscle. Although a significant proportion of familial ALS results from a toxic gain of function associated with dominant SOD1 mutations, the etiology of the disease and its specific cellular origins have remained difficult to define. Here, we show that muscle-restricted expression of a localized insulin-like growth factor (Igf) -1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1G93A transgenic mice, inducing calcineurin-mediated regenerative pathways. Muscle-specific expression of local Igf-1 (mIgf-1) isoform also stabilized neuromuscular junctions, reduced inflammation in the spinal cord, and enhanced motor neuronal survival in SOD1G93A mice, delaying the onset and progression of the disease. These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival.

Abbreviations used in this paper: AChR, acetylcholine receptor; ALS, amyotrophic lateral sclerosis; CnA, calcineurin; GFAP, glial fibrillary acidic protein; Igf, insulin-like growth factor; mIgf-1, local isoform of Igf-1; MyHC, myosin heavy chain; SOD1, superoxide dismutase1; wt, wild-type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents