Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.
Nat Neurosci. 2013 Nov;16(11):1530-6. doi: 10.1038/nn.3379. Epub 2013 Apr 14.
De novo protein synthesis is necessary for long-lasting modifications in synaptic strength and dendritic spine dynamics that underlie cognition. Fragile X syndrome (FXS), characterized by intellectual disability and autistic behaviors, holds promise for revealing the molecular basis for these long-term changes in neuronal function. Loss of function of the fragile X mental retardation protein (FMRP) results in defects in synaptic plasticity and cognition in many models of the disease. FMRP is a polyribosome-associated RNA-binding protein that regulates the synthesis of a set of plasticity-reated proteins by stalling ribosomal translocation on target mRNAs. The recent identification of mRNA targets of FMRP and its upstream regulators, and the use of small molecules to stall ribosomes in the absence of FMRP, have the potential to be translated into new therapeutic avenues for the treatment of FXS.
从头蛋白质合成对于支持认知的突触强度和树突棘动力学的持久改变是必要的。脆性 X 综合征（FXS）以智力障碍和自闭症行为为特征，有望揭示神经元功能这些长期变化的分子基础。脆性 X 智力迟钝蛋白（FMRP）的功能丧失导致疾病的许多模型中的突触可塑性和认知缺陷。FMRP 是一种多核糖体相关的 RNA 结合蛋白，通过在靶 mRNA 上阻滞核糖体易位来调节一组与可塑性相关的蛋白质的合成。最近鉴定了 FMRP 及其上游调节剂的 mRNA 靶标，以及使用小分子在没有 FMRP 的情况下阻滞核糖体，这有可能转化为治疗 FXS 的新治疗途径。
