| First Author | Tejero R | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 2 | Pages | 100826 |
| PubMed ID | 31981925 | Mgi Jnum | J:284105 |
| Mgi Id | MGI:6388728 | Doi | 10.1016/j.isci.2020.100826 |
| Citation | Tejero R, et al. (2020) R-Roscovitine Improves Motoneuron Function in Mouse Models for Spinal Muscular Atrophy. iScience 23(2):100826 |
| abstractText | 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 Ca(2+) 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 Ca(2+) signaling and Ca(2+) homeostasis in Smn-deficient motoneurons, which is generally crucial for motoneuron differentiation, maturation, and function. |
