2026-04-17T08:08:58Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1725502025-12-05T09:24:37Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478906col_2072_478917col_2072_478929
RECERCAT author Jorge Torres, Olga C. author Szczesna, Karolina author Roa, Laura author Casal, Carmen author Gonzalez Somermeyer, Louisa author Soler, Marta author Velasco, Cecilia D. author Martinez San Segundo, Pablo author Petazzi, Paolo author Sáez, Mauricio A. author Delgado Morales, Raul author Fourcade, Stéphane author Pujol Onofre, Aurora author Huertas, Dori author Llobet Berenguer, Artur, 1972- author Guil, Sonia author Esteller, Manel 2020-12-03T14:39:03Z2020-12-03T14:39:03Z2018-05-082020-12-03T14:39:03Z Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG- binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763. cc-by (c) Jorge-Torres, Olga C. et al., 2018 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess Síndrome de Rett Enginyeria de proteïnes Rett syndrome Protein engineering Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion