Calpain system is altered in survival motor neuron-reduced cells from in vitro and in vivo spinal muscular atrophy models
MetadataShow full item record
Spinal 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.
Is part ofCell Death & Disease, 2020, vol. 11, núm. 487
European research projects
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as cc-by (c) Fuente Ruiz, Sandra de la et al., 2020
Showing items related by title, author, creator and subject.
Spinal Muscular Atrophy autophagy profle is tissue-dependent: diferential regulation between muscle and motoneurons Sansa Zaragoza, Alba; Hidalgo, Iván; Miralles, Maria P.; Fuente Ruiz, Sandra de la; Pérez García, María José; Munell, Francina; Soler i Tatché, Rosa Ma.; Garcera, Ana (BioMed Central, 2021)Spinal muscular atrophy (SMA) is a neuromuscular genetic disease caused by reduced survival motor neuron (SMN) protein. SMN is ubiquitous and defcient levels cause spinal cord motoneurons (MNs) degeneration and muscle atrophy. ...
Intracellular pathways involved in cell survival are deregulated in mouse and human spinal muscular atrophy motoneurons Sansa Zaragoza, Alba; Fuente Ruiz, Sandra de la; Comella i Carnicé, Joan Xavier; Garcera, Ana; Soler i Tatché, Rosa Ma. (Elsevier, 2021-04-13)Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder caused by loss of the Survival Motor Neuron 1 gene (SMN1). Due to this depletion of the survival motor neuron (SMN) protein, the disease is characterized by ...
Calpain Inhibition Increases SMN Protein in Spinal Cord Motoneurons and Ameliorates the Spinal Muscular Atrophy Phenotype in Mice Fuente Ruiz, Sandra de la; Sansa Zaragoza, Alba; Periyakaruppiah, Ambika; Garcera, Ana; Soler i Tatché, Rosa Ma. (Springer Verlag, 2018)Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is caused by the loss of survival motor neuron 1 (SMN1) gene. SMA is characterized by the degeneration and loss of spinal cord motoneurons (MNs), ...