title: Muscle atrophy induced by SOD1G93A expression does not involve the activation of caspase in the absence of denervation.
abstract: BACKGROUND
  The most remarkable feature of skeletal muscle is the capacity to adapt its morphological, biochemical and molecular properties in response to several factors. Nonetheless, under pathological conditions, skeletal muscle loses its adaptability, leading to atrophy or wasting. Several signals might function as physiopathological triggers of muscle atrophy. However, the specific mechanisms underlying the atrophic phenotype under different pathological conditions remain to be fully elucidated. In this paper, we address the involvement of caspases in the induction of muscle atrophy in experimental models of amyotrophic lateral sclerosis (ALS) expressing the mutant SOD1G93A transgene either locally or ubiquitously.
  
  
  RESULTS
  We demonstrate that SOD1G93A-mediated muscle atrophy is independent from caspase activity. In particular, the expression of SOD1G93A promotes a reduction of the phosphatidylinositol 3-kinase/Akt pathway associated with activation of forkhead box O3. In contrast, the activation of caspases occurs later and is causally linked to motor neuron degeneration, which is associated with exacerbation of the atrophic phenotype and a shift in fiber-type composition.
  
  
  CONCLUSIONS
  This study suggests that muscle atrophy induced by the toxic effect of SOD1G93A is independent from the activation of apoptotic markers and that caspase-mediated apoptosis is a process activated upon muscle denervation.
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM; Sapienza University of Rome, Via A. Scarpa, 14 Rome I-00161, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dobrowolny
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM; Sapienza University of Rome, Via A. Scarpa, 14 Rome I-00161, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Aucello
authors.affiliation: Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM; Sapienza University of Rome, Via A. Scarpa, 14 Rome I-00161, Italy.|School of Biomedical & Sports Science; Unit of Human Biology, Edith Cowan University, Western Australia, Australia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò