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

I Gantois; A Khoutorsky; J Popic; A Aguilar-Valles; E Freemantle; R Cao; V Sharma; T Pooters; A Nagpal; A Skalecka; VT Truong; S Wiebe; IA Groves; Seyed Mehdi Jafarnejad Shourkaei; Clément  Chapat; Elizabeth A  McCullagh; Karine  Gamache; Karim  Nader; Jean-Claude  Lacaille; Christos G  Gkogkas; N Sonenberg

doi:10.1038/nm.4335

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

I Gantois, A Khoutorsky, J Popic, A Aguilar-Valles, E Freemantle, R Cao, V Sharma, T Pooters, A Nagpal, A Skalecka, VT Truong, S Wiebe, IA Groves, Seyed Mehdi Jafarnejad Shourkaei, Clément Chapat, Elizabeth A McCullagh, Karine Gamache, Karim Nader, Jean-Claude Lacaille, Christos G GkogkasN Sonenberg

Research output: Contribution to journal › Article › peer-review

166 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1-7
Journal	Nature Medicine
Early online date	15 May 2017
DOIs	https://doi.org/10.1038/nm.4335
Publication status	Published - 06 Jun 2017
Externally published	Yes

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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 Shourkaei, 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, 1-7. https://doi.org/10.1038/nm.4335

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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 = "I Gantois and A Khoutorsky and J Popic and A Aguilar-Valles and E Freemantle and R Cao and V Sharma and T Pooters and A Nagpal and A Skalecka and VT Truong and S Wiebe and IA Groves and {Jafarnejad Shourkaei}, {Seyed Mehdi} and Cl{\'e}ment Chapat and McCullagh, {Elizabeth A} and Karine Gamache and Karim Nader and Jean-Claude Lacaille and Gkogkas, {Christos G} and N Sonenberg",

year = "2017",

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doi = "10.1038/nm.4335",

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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 Shourkaei, SM, Chapat, C, McCullagh, EA, Gamache, K, Nader, K, Lacaille, J-C, Gkogkas, CG & Sonenberg, N 2017, 'Metformin ameliorates core deficits in a mouse model of fragile X syndrome.', Nature Medicine, pp. 1-7. https://doi.org/10.1038/nm.4335

TY - JOUR

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

AU - Gantois, I

AU - Khoutorsky, A

AU - Popic, J

AU - Aguilar-Valles, A

AU - Freemantle, E

AU - Cao, R

AU - Sharma, V

AU - Pooters, T

AU - Nagpal, A

AU - Skalecka, A

AU - Truong, VT

AU - Wiebe, S

AU - Groves, IA

AU - Jafarnejad Shourkaei, 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, N

PY - 2017/6/6

Y1 - 2017/6/6

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.

UR - http://europepmc.org/abstract/med/28504725

U2 - 10.1038/nm.4335

DO - 10.1038/nm.4335

M3 - Article

C2 - 28504725

SN - 1078-8956

SP - 1

EP - 7

JO - Nature Medicine

JF - Nature Medicine

ER -

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

Abstract

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