Molecular Signatures of Amyotrophic Lateral Sclerosis Disease Progression in Hind and Forelimb Muscles of an SOD1(G93A) Mouse Model (Articolo in rivista)

Type
Label
  • Molecular Signatures of Amyotrophic Lateral Sclerosis Disease Progression in Hind and Forelimb Muscles of an SOD1(G93A) Mouse Model (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1089/ars.2012.4524 (literal)
Alternative label
  • Daniele Capitanio; Michele Vasso,; Antonia Ratti; Giuliano Grignaschi; Manuela Volta; Manuela Moriggi; Cristina Daleno; Caterina Bendotti; Vincenzo Silani; Cecilia Gelfi. (2012)
    Molecular Signatures of Amyotrophic Lateral Sclerosis Disease Progression in Hind and Forelimb Muscles of an SOD1(G93A) Mouse Model
    in Antioxidants & redox signalling
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Daniele Capitanio; Michele Vasso,; Antonia Ratti; Giuliano Grignaschi; Manuela Volta; Manuela Moriggi; Cristina Daleno; Caterina Bendotti; Vincenzo Silani; Cecilia Gelfi. (literal)
Pagina inizio
  • 1333 (literal)
Pagina fine
  • 1350 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://online.liebertpub.com/doi/abs/10.1089/ars.2012.4524 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 17 (literal)
Rivista
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  • 10 (literal)
Note
  • PubMe (literal)
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  • Department of Biomedical Sciences for Health, University of Milan, Segrate, Italy. Institute of Molecular Bioimaging and Physiology, National Research Council, Segrate, Italy. Department of Neurology and Laboratory of Neuroscience, ''Dino Ferrari'' Center, University of Milan, IRCCS Italian Institute for Auxology, Milan, Italy. Laboratory of Molecular Neurobiology, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy. (literal)
Titolo
  • Molecular Signatures of Amyotrophic Lateral Sclerosis Disease Progression in Hind and Forelimb Muscles of an SOD1(G93A) Mouse Model (literal)
Abstract
  • Aims: This study utilized proteomics, biochemical and enzymatic assays, and bioinformatics tools that characterize protein alterations in hindlimb (gastrocnemius) and forelimb (triceps) muscles in an amyotrophic lateral sclerosis (ALS) (SOD1(G93A)) mouse model. The aim of this study was to identify the key molecular signatures involved in disease progression. Results: Both muscle types have in common an early down-regulation of complex I. In the hindlimb, early increases in oxidative metabolism are associated with uncoupling of the respiratory chain, an imbalance of NADH/NAD(+), and an increase in reactive oxygen species (ROS) production. The NADH overflow due to complex I inactivation induces TCA flux perturbations, leading to citrate production, triggering fatty acid synthase (FAS), and lipid peroxidation. These early metabolic changes in the hindlimb followed by sustained and comparatively higher metabolic and cytoskeletal derangements over time precede and may catalyze the progressive muscle wasting in this muscle at the late stage. By contrast, in the forelimb, there is an early down-regulation of complexes I and II that is associated with the reduction of oxidative metabolism, which promotes metabolic homeostasis that is accompanied by a greater cytoskeletal stabilization response. However, these early compensatory systems diminish by a later time point. Innovation: The identification of potential early- and late-stage disease molecular signatures in an ALS model: muscle albumin, complex I, complex II, citrate synthase, FAS, and phosphoinositide 3-kinase functions as diagnostic markers and peroxisome proliferator-activated receptor ? co-activator 1? (PGC1?), Sema-3A, and Rho-associated protein kinase 1 (ROCK1) play the role of disease progression markers. Conclusion: The differing pattern of cellular metabolism and cytoskeletal derangements in the hind and forelimb identifies the potential dysmetabolism/hypermetabolism molecular signatures associated with disease progression, which may serve as diagnostic/disease progression markers in ALS patients. (literal)
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