Pozzo-Miller Lucas, Pati Sandipan, Percy Alan K
Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, AL, USA.
Neurotherapeutics. 2015 Jul;12(3):631-40. doi: 10.1007/s13311-015-0353-y.
Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT.
雷特综合征（RTT）是一种由MECP2功能丧失突变引起的综合征性自闭症谱系障碍。甲基CpG结合蛋白2在靶基因启动子区域的CpG位点结合甲基胞嘧啶和5-羟甲基胞嘧啶，通过招募共抑制因子和共激活因子来控制它们的转录。在小鼠模型中进行的几项临床前研究已经确定了旨在纠正潜在神经功能障碍的药物治疗的合理分子靶点。这些靶向治疗正越来越多地转化为人体临床试验。在这篇综述中，我们概述了雷特综合征，并描述了基于甲基CpG结合蛋白2的小鼠模型的临床前研究现状，以及雷特综合征患者目前的临床试验情况。
