GABA受体与脆性X染色体综合征研究新进展  

Advance in GABA Receptors and Fragile X Syndrome

作　　者：张文华[1] 王云云[1] 丁明柳 刘剑峰[1] 

机构地区：[1]华中科技大学生命科学与技术学院,分子生物物理教育部重点实验室,武汉430074

出　　处：《生物物理学报》2013年第11期793-800,共8页Acta Biophysica Sinica

基　　金：国家自然科学基金重点项目(31130028);国家杰出青年科学基金项目(31225011)~~

摘　　要：脆性X染色体综合征(fragile X syndrome,FXS)是由于fmr1基因沉默导致脆性X精神迟滞蛋白(fragile X mental retardation protein,FMRP)表达不足而引起的一种常见的遗传性精神发育迟滞疾病。除了导致智力障碍外,FXS不同个体在临床还表现出神经发育障碍导致的其它缺陷,如注意力缺陷、多动症、自闭症、语言障碍和攻击性行为等。目前,其治疗手段主要集中在对FMRP调节的下游基因或蛋白信号的恢复和缓解上,但并不能够完全治愈。现有的针对FXS疾病的药物靶点除了I型代谢型谷氨酸受体(metabtropic glutamate receptors,mGluRs)外,近几年研究表明,γ-氨基丁酸(γ-aminobutyric acid,GABA)受体的激动剂也在动物模型和临床实验中表现出显著的效果。本文就GABA受体在FXS中的作用进展进行综述。The fragile X syndrome is the most common inherited cause of intellectual disability, resulting from the silencing of the fmrl gene which in turn lose FMRP expression. In addition to causing intellectual disability, FXS patients also exhibit other symptoms, such as attention deficit, hyperactivity, autism, language impairments and aggression. Now the main treatment strategy is focused on rescuing the downstream gene or protein signaling of FMRP, but the treatment efficacy is limited. The widely used drug targets for the FXS disease is group I mGluRs. However, recent studies indicate that agonists of GABA receptors showed a significant effect both in animal models and clinical trials. Here the authors review the role of GABA receptors in the fragile X syndrome.

关 键 词：脆性X综合征 脆性X精神迟滞蛋白 MGLUR GABAA受体 GABAB受体 

分 类 号：Q25[生物学—细胞生物学] Q291