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Título : Restoration of myogenesis in ALS-myocytes through miR-26a-5p-mediated Smad4 inhibition and its impact on motor neuron development
Autor : Peggion, Caterina
Bonadio, Raphael Severino
Stella, Roberto
Scalabrin, Silvia
Pasetto, Laura
Millino, Caterina
Camporeale, Laura
Pacchioni, Beniamina
Bonetto, Valentina
Bertoli, Alessandro
Cagnin, Stefano
Massimino, Maria Lina
metadata.dc.identifier.orcid: https://orcid.org/0000-0002-9967-2629
https://orcid.org/0000-0002-4832-2776
https://orcid.org/0000-0003-1462-4423
https://orcid.org/0009-0000-3604-8792
https://orcid.org/0000-0003-0319-4448
https://orcid.org/0000-0003-0456-2054
https://orcid.org/0000-0003-1202-0191
metadata.dc.contributor.affiliation: University of Padova, Department of Biology
University of Padova, Department of Biology
Istituto Zooprofilattico Sperimentale delle Venezie, Department of Chemistry
University of Padova, Department of Biology
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Research Center for ALS
University of Padova, Department of Biology
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Research Center for ALS
University of Padova, Department of Biology
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Research Center for ALS
University of Padova, Department of Biomedical Sciences
University of Padova, Padova Neuroscience Center
National Research Council (CNR), Section of Padova, Neuroscience Institute
University of Padova, Department of Biology
University of Padova, CIR-Myo Myology Center
National Research Council (CNR), Section of Padova, Neuroscience Institute
Assunto:: RNAs não-codificadores
Esclerose lateral amiotrófica
Doenças neuromusculares
Músculo esquelético
Fecha de publicación : 30-may-2025
Editorial : Elsevier
Citación : PEGGION, Caterina et al. Restoration of myogenesis in ALS-myocytes through miR-26a-5p-mediated Smad4 inhibition and its impact on motor neuron development. Molecular Therapy: Nucleic Acids, v. 36, n. 3, e102581, 2025. DOI: https://doi.org/10.1016/j.omtn.2025.102581. Disponível em: https://www.sciencedirect.com/science/article/pii/S2162253125001350?via%3Dihub. Acesso em: 27 jan. 2026.
Abstract: Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder, characterized primarily by a progressive loss of motor neurons (MNs) in which degeneration skeletal muscle involvement has been demonstrated. Skeletal muscle is a plastic tissue that responds to insults through proliferation and differentiation of satellite cells. Skeletal muscle degeneration and regeneration are finely regulated by signals that regulate satellite cell proliferation and differentiation. It is known that satellite cell differentiation is impaired in ALS, but little is known about the involvement of microRNAs (miRNAs) and their role in intercellular communication in ALS. Here we demonstrated impaired differentiation of satellite cells derived from ALS mice related to the impairment of myogenic p38MAPK and protein kinase A (PKA)/pCREB signaling pathways that can be regulated by miR-882 and -134-5p. These miRNAs participate in autocrine signaling in association with miR-26a-5p that, secreted from wild-type (WT) and captured by ALS myoblasts, enhances ALS-related myoblast differentiation by repressing Smad4-related signals. Moreover, miR-26a-5p and -431-5p work in a paracrine way ameliorating motoneuron differentiation. These findings emphasize the need to better understand intercellular communication and its role in ALS pathogenesis and progression. They also suggest that miRNAs could be targeted or used as therapeutic agents for myofiber and MN regeneration.
metadata.dc.description.unidade: Instituto de Ciências Biológicas (IB)
Departamento de Genética e Morfologia (IB GEM)
Licença:: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI: https://doi.org/10.1016/j.omtn.2025.102581
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