Metformin ameliorates core deficits in a mouse model of fragile X syndrome
I Gantois, A Khoutorsky, J Popic, A Aguilar-Valles… - Nature medicine, 2017 - nature.com
Nature medicine, 2017•nature.com
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.
(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.
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.
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