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dc.contributor.authorFuente Ruiz, Sandra de la
dc.contributor.authorSansa Zaragoza, Alba
dc.contributor.authorHidalgo, Iván
dc.contributor.authorVivancos, Nuria
dc.contributor.authorRomero-Guevara, Ricardo
dc.contributor.authorGarcera, Ana
dc.contributor.authorSoler i Tatché, Rosa Ma.
dc.description.abstractSpinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by loss of the survival motor neuron 1 (SMN1) gene. SMA is characterized by the degeneration of spinal cord motoneurons (MNs), progressive skeletal muscle atrophy, and weakness. The cellular and molecular mechanisms causing MN loss of function are only partially known. Recent advances in SMA research postulate the role of calpain protease regulating survival motor neuron (SMN) protein and the positive effect on SMA phenotype of treatment with calpain inhibitors. We analyzed the level of calpain pathway members in mice and human cellular SMA models. Results indicate an increase of calpain activity in SMN-reduced MNs. Spinal cord analysis of SMA mice treated with calpeptin, a calpain inhibitor, showed an increase of SMN, calpain, and its endogenous inhibitor calpastatin in MNs. Finally, in vitro calpeptin treatment prevented microtubule-associated protein 1A/1B-light chain 3 (LC3) increase in MNs neurites, indicating that calpain inhibition may reduce autophagosome accumulation in neuron prolongations, but not in soma. Thus, our results show that calpain activity is increased in SMA MNs and its inhibition may have a beneficial effect on SMA phenotype through the increase of SMN in spinal cord MNs.
dc.description.sponsorshipThis work was supported by grants from Instituto de Salud Carlos III, Fondo de Inversiones Sanitarias, Unión Europea, Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” (PI17/00231 and PI17/00134). CERCA Program/Generalitat de Catalunya. SdF holds a fellowship from Universitat de Lleida and “Ajuts de Promoció de la Recerca en Salut 2018” (IRBLLEIDA-Diputació de Lleida). AS holds a fellowship from Universitat de Lleida. AG holds a postdoctoral fellowship from Universitat de Lleida. We thank Dr. Manuel Portero from Metabolic Physiopathology Group, Universitat de Lleida-IRBLLEIDA for human iPSC differentiation protocol and assistance. We thank Elaine Lilly, PhD, for English language revision of the paper.
dc.publisherSpringer Nature
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofCell Death & Disease, 2020, vol. 11, núm. 487
dc.rightscc-by (c) Fuente Ruiz, Sandra de la et al., 2020
dc.subject.otherAtròfia muscular espinal
dc.titleCalpain system is altered in survival motor neuron-reduced cells from in vitro and in vivo spinal muscular atrophy models

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cc-by (c) Fuente Ruiz, Sandra de la et al., 2020
Except where otherwise noted, this item's license is described as cc-by (c) Fuente Ruiz, Sandra de la et al., 2020