Artículo
R-Roscovitine Improves Motoneuron Function in Mouse Models for Spinal Muscular Atrophy
Autor/es | Tejero, Rocío
Balk, Stefanie Franco-Espin, Julio Ojeda Orellana, Jorge Hennlein, Luisa Drexl, Hans Tabares, Lucía Jablonka, Sibylle |
Director | |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2020-02-21 |
Fecha de depósito | 2023-05-15 |
Publicado en |
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Resumen | 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 ... 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. |
Cita | 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. |
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