Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which l...Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.展开更多
脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,...脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,其中先证者伴有罕见的晚发性癫痫发作,经左乙拉西坦治疗效果良好,而其弟弟经反复随访未见脑电图异常。该对病例提示FXS临床表型具有多样性和异质性。展开更多
文摘Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.
文摘脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,其中先证者伴有罕见的晚发性癫痫发作,经左乙拉西坦治疗效果良好,而其弟弟经反复随访未见脑电图异常。该对病例提示FXS临床表型具有多样性和异质性。
