Dysregulation and restoration of translational homeostasis in fragile X syndrome.
Dysregulation and restoration of translational homeostasis in fragile X syndrome.
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DOI：
10.1038/nrn4001
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Klann E
中科院分区：
文献类型：
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作者：
Richter JD;Bassell GJ;Klann E
脆性X综合征(FXS)是最常见的遗传性智力残疾形式，也是自闭症最常见的单基因原因，其原因是缺乏脆性X智力低下蛋白(FMRP)，FMRP是一种RNA结合蛋白，在大多数情况下起到抑制翻译的作用。针对受体、支架蛋白、激酶和翻译控制蛋白的多种药物和遗传操作可以挽救FXS模型小鼠的神经元形态、突触功能和行为表型，可能是通过将过度的神经元翻译减少到正常水平。未来还可能探索这样的救援策略，以确定对FXS病理生理学至关重要的mRNAs。
Fragile X syndrome (FXS), the most-frequently inherited form of intellectual disability and the most-prevalent single-gene cause of autism, results from a lack of fragile X mental retardation protein (FMRP), an RNA-binding protein that acts, in most cases, to repress translation. Multiple pharmacological and genetic manipulations that target receptors, scaffolding proteins, kinases and translational control proteins can rescue neuronal morphology, synaptic function and behavioural phenotypes in FXS model mice, presumably by reducing excessive neuronal translation to normal levels. Such rescue strategies might also be explored in the future to identify the mRNAs that are critical for FXS pathophysiology.