The inhibition of CTGF/CCN2 activity improves muscle and locomotor function in a murine ALS model

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dc.contributor.authorGonzález, David
dc.contributor.authorCorrea, Lina M.
dc.contributor.authorCourt, Felipe A.
dc.contributor.authorCerpa, Waldo
dc.contributor.authorLipson, Kenneth E.
dc.contributor.authorVan Zundert, Brigitte
dc.contributor.authorBrandan, Enrique
dc.contributor.authorRebolledo, Daniela L.
dc.date.accessioned2022-07-07T23:13:12Z
dc.date.available2022-07-07T23:13:12Z
dc.date.issued2018-08
dc.descriptionIndexación Scopuses
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a devastating adult-onset progressive neurodegenerative disease characterized by upper and lower motoneuron degeneration. A total of 20% of familial ALS (fALS) cases are explained by mutations in the superoxide dismutase 1 (SOD1) enzyme. Although more than 20 years have passed since the generation of the first ALS mouse model, the precise molecular mechanisms of ALS pathogenesis remain unknown. CTGF/CCN2 is a matricellular protein with associated fibrotic activity that is up-regulated in several chronic diseases. The inhibition of CTGF/CCN2 with the monoclonal neutralizing antibody FG-3019 reduces fibrosis in several chronic disorders including the mdx mice, a murine model for Duchenne muscular dystrophy (DMD). In this work, we show that there are increased levels of CTGF/CCN2 in skeletal muscle and spinal cord of hSOD1G93A mice. In this scenario, we show evidence that FG-3019 not only reduces fibrosis in skeletal muscle of hSOD1G93A mice, but also improves muscle and locomotor performance. We demonstrate that treatment with FG-3019 reduces muscle atrophy in hSOD1G93A mice. We also found improvement of neuromuscular junction (NMJ) innervation together with a reduction in myelin degeneration in the sciatic nerve, suggesting that alterations in nerve-muscle communication are partially improved in FG-3019-treated hSOD1G93A mice. Moreover, we also found that CTGF/CCN2 is expressed in astrocytes and neurons, predominantly in dorsal areas of spinal cord from symptomatic hSOD1G93A mice. Together, these results reveal that CTGF/CCN2 might be a novel therapeutic target to ameliorate symptoms and improve the quality of life of ALS patients. © The Author(s) 2018.es
dc.description.urihttps://academic-oup-com.recursosbiblioteca.unab.cl/hmg/article/27/16/2913/5025678
dc.identifier.citationHuman Molecular Genetics Volume 27, Issue 16, Pages 2913 - 292615 August 2018es
dc.identifier.doi10.1093/hmg/ddy204
dc.identifier.issn09646906
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/23217
dc.language.isoenes
dc.publisherOxford University Presses
dc.rights.licenseCC BY 4.0
dc.subjectSignal Transductiones
dc.subjectCysteine Rich Protein 61es
dc.subjectCCN Proteines
dc.titleThe inhibition of CTGF/CCN2 activity improves muscle and locomotor function in a murine ALS modeles
dc.typeArtículoes
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