RESUMO
CDKL5 mutation is associated with an atypical Rett syndrome (RTT) variant. Recently, cholesterol homeostasis perturbation and oxidative-mediated loss of the high-density lipoprotein receptor SRB1 in typical RTT have been suggested. Here, we demonstrate an altered lipid serum profile also in CDKL5 patients with decreased levels of SRB1 and impaired activation of the defensive system Nrf2. In addition, CDKL5 fibroblasts showed an increase in 4-hydroxy-2-nonenal- and nitrotyrosine-SRB1 adducts that lead to its ubiquitination and probable degradation. This study highlights a possible common denominator between two different RTT variants (MECP2 and CDKL5) and a possible common future therapeutic target.
Assuntos
Lipídeos/sangue , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Serina-Treonina Quinases/genética , Síndrome de Rett/genética , Receptores Depuradores Classe B/genética , Espasmos Infantis/genética , Adolescente , Células Cultivadas , Criança , Pré-Escolar , Síndromes Epilépticas , Feminino , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Síndrome de Rett/sangue , Receptores Depuradores Classe B/metabolismo , Espasmos Infantis/sangue , Regulação para CimaRESUMO
The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.freeradbiomed.2013.09.018. The duplicate article has therefore been withdrawn.