RT info:eu-repo/semantics/doctoralThesis
T1 The anticonvulsant and neuroprotective roles of sgk1.1
A1 Martín Batista, Elva
A2 Programa de Doctorado en Ciencias de la Salud
K1 Fisiología humana
K1 Neuropatologías
K1 Genética molecular
K1 Sistema nervioso central
AB Epilepsy is a neurological disease that affects more than 50 million people around the world. It is characterized by recurrent seizures, the most extreme form of synchronous brain activity. In the nervous system, Kv7 channels are responsible for the M-current, which is important to regulate neuronal excitability. Our laboratory has previously described a new modulator of Kv7.2/3 channels, the neuronal isoform of SGK1 kinase, SGK1.1, which up-regulates channel activity and counteracts hyperexcitability. Using a kainic acid-induced model of temporal lobe epilepsy with transgenic mice expressing a constitutively active form of SGK1.1, we have demonstrated that this kinase is a potent anticonvulsant factor, shortening seizure severity and duration independently of age, sex and genetic background. Furthermore, we show that SGK1.1 drastically reduces seizure-induced neuronal death and associated gliosis through M current-dependent and -independent mechanisms. In addition, our results demonstrate that constitutively active SGK1.1 is able to up-regulate Kv7 channels harboring epilepsy-causing mutations. Altogether, our results establish SGK1.1 as a new potential therapeutic target for epilepsy treatment.
YR 2021
FD 2021
LK http://riull.ull.es/xmlui/handle/915/27328
UL http://riull.ull.es/xmlui/handle/915/27328
LA en
NO Ministerio de Ciencia, Innovación y Universidades (BFU2015-66490-R, BES-2016-077337)
DS Repositorio institucional de la Universidad de La Laguna
RD 18-nov-2024