Metformin ameliorates core deficits in a mouse model of fragile X syndrome

Autor:	Shane Wiebe, Karim Nader, Argel Aguilar-Valles, Vinh Tai Truong, Ilse Gantois, Seyed Mehdi Jafarnejad, Jean-Claude Lacaille, Clément Chapat, Nahum Sonenberg, Vijendra Sharma, Jelena Popic, Erika Freemantle, Christos G. Gkogkas, Isabelle A. Groves, Anmol Nagpal, Tine Pooters, Agnieszka Skalecka, Karine Gamache, Arkady Khoutorsky, Ruifeng Cao, Elizabeth A. McCullagh
Rok vydání:	2017
Předmět:	Male 0301 basic medicine MAPK/ERK pathway congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty endocrine system diseases MAP Kinase Signaling System Type 2 diabetes General Biochemistry Genetics and Molecular Biology Fragile X Mental Retardation Protein Mice 03 medical and health sciences 0302 clinical medicine Animals Hypoglycemic Agents Medicine RNA Messenger Phosphorylation Social Behavior Psychiatry Mice Knockout Behavior Animal business.industry EIF4E General Medicine medicine.disease FMR1 Metformin Fragile X syndrome Disease Models Animal Eukaryotic Initiation Factor-4E 030104 developmental biology Matrix Metalloproteinase 9 Fragile X Syndrome Cancer research Trinucleotide Repeat Expansion business Trinucleotide repeat expansion 030217 neurology & neurosurgery medicine.drug
Zdroj:	Gantois, I, Khoutorsky, A, Popic, J, Aguilar-Valles, A, Freemantle, E, Cao, R, Sharma, V, Pooters, T, Nagpal, A, Skalecka, A, Truong, V T, Wiebe, S, Groves, I A, Jafarnejad, S M, Chapat, C, McCullagh, E A, Gamache, K, Nader, K, Lacaille, J-C, Gkogkas, C G & Sonenberg, N 2017, ' Metformin ameliorates core deficits in a mouse model of fragile X syndrome ', Nature Medicine, vol. 23, pp. 674-677 . https://doi.org/10.1038/nm.4335
ISSN:	1546-170X 1078-8956
Popis:	Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1−/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f22dfc7b820d1427e3ff684679f6a038 https://doi.org/10.1038/nm.4335 Zobrazit plný text záznamu Full text from SpringerLink