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

Ilse Gantois; Arkady Khoutorsky; Jelena Popic; Argel Aguilar-Valles; Erika Freemantle; Ruifeng Cao; Vijendra Sharma; Tine Pooters; Anmol Nagpal; Agnieszka Skalecka; Vinh T. Truong; Shane Wiebe; Isabelle A. Groves; Seyed Mehdi Jafarnejad; Clément Chapat; Elizabeth A. McCullagh; Karine Gamache; Karim Nader; Jean Claude Lacaille; Christos G. Gkogkas; Nahum Sonenberg

doi:10.1038/nm.4335

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

Ilse Gantois
, Arkady Khoutorsky
, Jelena Popic
, Argel Aguilar-Valles
, Erika Freemantle
, Ruifeng Cao
, Vijendra Sharma
, Tine Pooters
, Anmol Nagpal
, Agnieszka Skalecka
, Vinh T. Truong
, Shane Wiebe
, Isabelle A. Groves
, Seyed Mehdi Jafarnejad
, Clément Chapat
, Elizabeth A. McCullagh
, Karine Gamache
, Karim Nader
, Jean Claude Lacaille
, Christos G. Gkogkas

Nahum Sonenberg

McGill University
McGill University
McGill University
Universite de Montreal
University of Minnesota Medical School
University of Edinburgh
University of Edinburgh
University of Colorado School of Medicine

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

Résumé

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.

langue originale	Anglais
Pages (de - à)	674-677
Nombre de pages	4
journal	Nature Medicine
Volume	23
Numéro de publication	6
Les DOIs	https://doi.org/10.1038/nm.4335
état	Publié - 1 juin 2017
Modification externe	Oui

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10.1038/nm.4335

Contient cette citation

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., ... Sonenberg, N. (2017). Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nature Medicine, 23(6), 674-677. https://doi.org/10.1038/nm.4335

@article{2d3decfe73fb459482210fd90f4cca3a,

title = "Metformin ameliorates core deficits in a mouse model of fragile X syndrome",

abstract = "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.",

author = "Ilse Gantois and Arkady Khoutorsky and Jelena Popic and Argel Aguilar-Valles and Erika Freemantle and Ruifeng Cao and Vijendra Sharma and Tine Pooters and Anmol Nagpal and Agnieszka Skalecka and Truong, \{Vinh T.\} and Shane Wiebe and Groves, \{Isabelle A.\} and Jafarnejad, \{Seyed Mehdi\} and Cl{\'e}ment Chapat and McCullagh, \{Elizabeth A.\} and Karine Gamache and Karim Nader and Lacaille, \{Jean Claude\} and Gkogkas, \{Christos G.\} and Nahum Sonenberg",

year = "2017",

month = jun,

day = "1",

doi = "10.1038/nm.4335",

language = "English",

volume = "23",

pages = "674--677",

journal = "Nature Medicine",

issn = "1078-8956",

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}

Gantois, I, Khoutorsky, A, Popic, J, Aguilar-Valles, A, Freemantle, E, Cao, R, Sharma, V, Pooters, T, Nagpal, A, Skalecka, A, Truong, VT, Wiebe, S, Groves, IA, Jafarnejad, SM, Chapat, C, McCullagh, EA, Gamache, K, Nader, K, Lacaille, JC, Gkogkas, CG & Sonenberg, N 2017, 'Metformin ameliorates core deficits in a mouse model of fragile X syndrome', Nature Medicine, VOL. 23, Numéro 6, p. 674-677. https://doi.org/10.1038/nm.4335

TY - JOUR

T1 - Metformin ameliorates core deficits in a mouse model of fragile X syndrome

AU - Gantois, Ilse

AU - Khoutorsky, Arkady

AU - Popic, Jelena

AU - Aguilar-Valles, Argel

AU - Freemantle, Erika

AU - Cao, Ruifeng

AU - Sharma, Vijendra

AU - Pooters, Tine

AU - Nagpal, Anmol

AU - Skalecka, Agnieszka

AU - Truong, Vinh T.

AU - Wiebe, Shane

AU - Groves, Isabelle A.

AU - Jafarnejad, Seyed Mehdi

AU - Chapat, Clément

AU - McCullagh, Elizabeth A.

AU - Gamache, Karine

AU - Nader, Karim

AU - Lacaille, Jean Claude

AU - Gkogkas, Christos G.

AU - Sonenberg, Nahum

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

U2 - 10.1038/nm.4335

DO - 10.1038/nm.4335

M3 - Article

C2 - 28504725

AN - SCOPUS:85020311542

SN - 1078-8956

VL - 23

SP - 674

EP - 677

JO - Nature Medicine

JF - Nature Medicine

IS - 6

ER -

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

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