América Chandía-Cristi, Daniela A Gutiérrez, Andrés E Dulcey, Marcelo Lara, Lina Vargas, Yi-Han Lin, Pablo Jimenez-Muñoz, Gabriela Larenas, Xin Xu, Amy Wang, Ashley Owens, Christopher Dextras, YuChi Chen, Claudio Pinto, Tamara Marín, Hugo Almarza-Salazar, Keryma Acevedo, Gonzalo I Cancino, Xin Hu, Patricio Rojas, Marc Ferrer, Noel Southall, Mark J Henderson, Silvana Zanlungo, Juan J Marugan, Alejandra Álvarez R
The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival...
April 23, 2024: Cell Reports