dc.contributor.advisor | | |
dc.creator | Tejero, Rocío | es |
dc.creator | Balk, Stefanie | es |
dc.creator | Franco-Espin, Julio | es |
dc.creator | Ojeda Orellana, Jorge | es |
dc.creator | Hennlein, Luisa | es |
dc.creator | Drexl, Hans | es |
dc.creator | Tabares, Lucía | es |
dc.creator | Jablonka, Sibylle | es |
dc.date.accessioned | 2023-05-15T13:46:13Z | |
dc.date.available | 2023-05-15T13:46:13Z | |
dc.date.issued | 2020-02-21 | |
dc.identifier.citation | Tejero, R., Balk, S., Franco-Espin, J., Ojeda Orellana, J., Hennlein, L., Drexl, H.,...,Jablonka, S. (2020). R-Roscovitine Improves Motoneuron Function in Mouse Models for Spinal Muscular Atrophy. iScience, 23 (2), 100826. https://doi.org/10.1016/j.isci.2020.100826. | |
dc.identifier.issn | 2589-0042 | es |
dc.identifier.other | https://www.sciencedirect.com/science/article/pii/S2589004220300092?via%3Dihub | |
dc.identifier.uri | https://hdl.handle.net/11441/146030 | |
dc.description.abstract | Neurotransmission defects and motoneuron degeneration are hallmarks of spinal muscular atrophy, a
monogenetic disease caused by the deficiency of the SMN protein. In the present study, we show that
systemic application of R-Roscovitine, a Cav2.1/Cav2.2 channel modifier and a cyclin-dependent kinase
5 (Cdk-5) inhibitor, significantly improved survival of SMA mice. In addition, R-Roscovitine increased
Cav2.1 channel density and sizes of the motor endplates. In vitro, R-Roscovitine restored axon lengths
and growth cone sizes of Smn-deficient motoneurons corresponding to enhanced spontaneous Ca2+
influx and elevated Cav2.2 channel cluster formations independent of its capability to inhibit Cdk-5.
Acute application of R-Roscovitine at the neuromuscular junction significantly increased evoked
neurotransmitter release, increased the frequency of spontaneous miniature potentials, and lowered
the activation threshold of silent terminals. These data indicate that R-Roscovitine improves Ca2+
signaling and Ca2+ homeostasis in Smn-deficient motoneurons, which is generally crucial for motoneuron differentiation, maturation, and function. | es |
dc.format | application/pdf | es |
dc.format.extent | 37 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | iScience, 23 (2), 100826. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | R-Roscovitine Improves Motoneuron Function in Mouse Models for Spinal Muscular Atrophy | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica | es |
dc.identifier.doi | 10.1016/j.isci.2020.100826 | es |
dc.journaltitle | iScience | es |
dc.publication.volumen | 23 | es |
dc.publication.issue | 2 | es |
dc.publication.initialPage | 100826 | es |