Pioglitazone improves deficits of Fmr1-KO mouse model of Fragile X syndrome by interfering with excessive diacylglycerol signaling - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2020

Pioglitazone improves deficits of Fmr1-KO mouse model of Fragile X syndrome by interfering with excessive diacylglycerol signaling

Karima Habbas
  • Fonction : Auteur
Boglarka Zambo
  • Fonction : Auteur
Laetitia Schramm
  • Fonction : Auteur
Arnaud Duchon
  • Fonction : Auteur
Eric Flatter
  • Fonction : Auteur
Laetitia Fouillen
Julie Zumsteg
  • Fonction : Auteur
Dimitri Heintz
Jean-Louis Mandel
  • Fonction : Auteur
Yann Hérault
Hervé Moine

Résumé

Fragile X syndrome (FXS), the leading cause of familial intellectual disability, is an uncured disease caused by the absence or loss of function of the FMRP protein. FMRP is an RNA binding protein that controls the translation of specific proteins in neurons. A main target of FMRP in neurons is diacylglycerol kinase kappa (DGKk) and the loss of FMRP leads to a loss of DGK activity causing a diacylglycerol excess in the brain. Excessive diacylglycerol signaling could be a significant contributor to the pathomechanism of FXS. Here we tested the contribution of DAG-signaling in Fmr1 -KO mouse model of FXS and we show that pioglitazone, a widely prescribed drug for type 2 diabetes, has ability to correct excessive DAG signaling in the brain and rescue behavioral alterations of the Fmr1 -KO mouse. This study highlights the role of lipid signaling homeostasis in FXS and provides arguments to support the testing of pioglitazone for treatment of FXS.
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Dates et versions

hal-03028259 , version 1 (27-11-2020)

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Andréa Geoffroy, Karima Habbas, Boglarka Zambo, Laetitia Schramm, Arnaud Duchon, et al.. Pioglitazone improves deficits of Fmr1-KO mouse model of Fragile X syndrome by interfering with excessive diacylglycerol signaling. 2020. ⟨hal-03028259⟩
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