Department of Cell and Molecular Physiology, UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Trends Neurosci. 2011 Jun;34(6):293-303. doi: 10.1016/j.tins.2011.04.001. Epub 2011 May 17.
Angelman syndrome (AS) is a severe genetic disorder caused by mutations or deletions of the maternally inherited UBE3A gene. UBE3A encodes an E3 ubiquitin ligase that is expressed biallelically in most tissues but is maternally expressed in almost all neurons. In this review, we describe recent advances in understanding the expression and function of UBE3A in the brain and the etiology of AS. We highlight current AS model systems, epigenetic mechanisms of UBE3A regulation, and the identification of potential UBE3A substrates in the brain. In the process, we identify major gaps in our knowledge that, if bridged, could move us closer to identifying treatments for this debilitating neurodevelopmental disorder.
天使综合征（AS）是一种严重的遗传疾病，由母系遗传的 UBE3A 基因突变或缺失引起。UBE3A 编码一种 E3 泛素连接酶，在大多数组织中均呈双等位基因表达，但在几乎所有神经元中均由母系表达。在这篇综述中，我们描述了近年来对 UBE3A 在大脑中的表达和功能以及 AS 病因的理解进展。我们重点介绍了当前的 AS 模型系统、UBE3A 调节的表观遗传机制以及大脑中潜在的 UBE3A 底物的鉴定。在此过程中，我们确定了我们知识中的主要空白，如果加以弥补，可能会使我们更接近确定治疗这种使人衰弱的神经发育障碍的方法。
