Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder
Towards a better diagnosis and treatment of Rett syndrome: a model synaptic disorder
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DOI：
10.1093/brain/awy323
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发表时间：
2019-02-01
期刊：
影响因子：
14.5
通讯作者：
Kaufmann, Walter E.
中科院分区：
文献类型：
--
作者：
Banerjee, Abhishek;Miller, Meghan T.;Kaufmann, Walter E.
随着Rett综合征首次发表50周年，以及Rett综合征与MECP2突变之间联系的首次报告近20年，重要的是要反思我们对这种神经发育障碍的诊断和治疗的理解及其意义的巨大进步。Rett综合征是生物学家和临床医生面临的一个有趣的挑战，因为这种疾病位于突触和回路中表观遗传调节和神经生理学改变的分子机制的交叉点，共同导致严重的病理生理学内表型。遗传学、临床和神经生物学证据支持Rett综合征主要是一种突触障碍，是智力残疾和自闭症谱系障碍的疾病模型。本文综述了Rett综合征最近的神经生物学和临床前研究结果的主要进展，以及它们在多大程度上开始影响我们对这种疾病的理解和管理。它还讨论了潜在的应用知识的突触可塑性异常Rett综合征的诊断和治疗。
With the recent 50th anniversary of the first publication on Rett syndrome, and the almost 20 years since the first report on the link between Rett syndrome and MECP2 mutations, it is important to reflect on the tremendous advances in our understanding and their implications for the diagnosis and treatment of this neurodevelopmental disorder. Rett syndrome features an interesting challenge for biologists and clinicians, as the disorder lies at the intersection of molecular mechanisms of epigenetic regulation and neurophysiological alterations in synapses and circuits that together contribute to severe pathophysiological endophenotypes. Genetic, clinical, and neurobiological evidences support the notion that Rett syndrome is primarily a synaptic disorder, and a disease model for both intellectual disability and autism spectrum disorder. This review examines major developments in both recent neurobiological and preclinical findings of Rett syndrome, and to what extent they are beginning to impact our understanding and management of the disorder. It also discusses potential applications of knowledge on synaptic plasticity abnormalities in Rett syndrome to its diagnosis and treatment.