title: Time-Point Dependent Activation of Autophagy and the UPS in SOD1G93A Mice Skeletal Muscle.
abstract: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by a selective loss of motor neurons together with a progressive muscle weakness. Albeit the pathophysiological mechanisms of the disease remain unknown, growing evidence suggests that skeletal muscle can be a target of ALS toxicity. In particular, the two main intracellular degradation mechanisms, autophagy and the ubiquitin-proteasome degradative system (UPS) have been poorly studied in this tissue. In this study we investigated the activation of autophagy and the UPS as well as apoptosis in the skeletal muscle from SOD1G93A mice along disease progression. Our results showed a significant upregulation of proteasome activity at early symptomatic stage, while the autophagy activation was found at presymptomatic and terminal stages. The mRNA upregulated levels of LC3, p62, Beclin1, Atg5 and E2f1 were only observed at symptomatic and terminal stages, which reinforced the time-point activation of autophagy. Furthermore, no apoptosis activation was observed along disease progression. The combined data provided clear evidence for the first time that there is a time-point dependent activation of autophagy and UPS in the skeletal muscle from SOD1G93A mice.
authors.affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Oliván
authors.affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Calvo
authors.affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Samanta
authors.initials: S
authors.lastname: Gasco
authors.affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Muñoz
authors.affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.affiliation: Laboratorio de Genética y Bioquímica (LAGENBIO), Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Osta
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D046988:Proteasome Endopeptidase Complex