二甲双胍改善脆性 X 综合征小鼠模型的核心缺陷。
Metformin ameliorates core deficits in a mouse model of fragile X syndrome.
机构信息
Department of Biochemistry, McGill University, Montréal, Québec, Canada.
Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada.
出版信息
Nat Med. 2017 Jun;23(6):674-677. doi: 10.1038/nm.4335. Epub 2017 May 15.
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 mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic.
脆性 X 综合征（FXS）是自闭症谱系障碍（ASD）的主要单基因病因。FMR1 中的三核苷酸重复扩增导致 FMRP 表达缺失，从而导致 ERK 和 mTOR 信号通路在上游 mRNA 翻译过程中过度激活。在这里，我们表明，二甲双胍，这是用于 2 型糖尿病的最广泛使用的药物，挽救了 Fmr1 小鼠的核心表型，并选择性地使 ERK 信号、eIF4E 磷酸化和 MMP-9 的表达正常化。因此，二甲双胍是一种潜在的 FXS 治疗药物。
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