Department of Cell and Molecular Physiology, Neuroscience Center, and Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA.
J Neurodev Disord. 2011 Mar;3(1):50-6. doi: 10.1007/s11689-010-9066-z. Epub 2010 Dec 3.
This report is a meeting summary of the 2010 Angelman Syndrome Foundation's scientific symposium on the neuroscience of UBE3A. Angelman syndrome is characterized by loss of speech, severe developmental delay, seizures, and ataxia. These core symptoms are caused by maternal allele disruptions of a single gene-UBE3A. UBE3A encodes an E3 ubiquitin ligase that targets certain proteins for proteasomal degradation. This biology has led to the expectation that the identification of Ube3a protein targets will lead to therapies for Angelman syndrome. The recent discovery of Ube3a substrates such as Arc (activity-regulated cytoskeletal protein) provides new insight into the mechanisms underlying the synaptic function and plasticity deficits caused by the loss of Ube3a. In addition to identifying Ube3a substrates, there have also been recent advances in understanding UBE3A's integrated role in the neuronal repertoire of genes and protein interactions. A developmental picture is now emerging whereby UBE3A gene dosage on chromosome 15 alters synaptic function, with deficiencies leading to Angelman syndrome and overexpression associated with classic autism symptomatology.
本报告是 2010 年安格曼综合征基金会神经科学 UBE3A 科学研讨会的会议总结。安格曼综合征的特征是丧失语言能力、严重发育迟缓、癫痫发作和共济失调。这些核心症状是由单基因 UBE3A 的母等位基因破坏引起的。UBE3A 编码一种 E3 泛素连接酶，可将特定蛋白质靶向蛋白酶体降解。这一生物学特性导致人们期望鉴定 Ube3a 蛋白靶标将为安格曼综合征的治疗带来新的希望。最近发现的 Ube3a 底物，如 Arc（活性调节细胞骨架蛋白），为 Ube3a 缺失引起的突触功能和可塑性缺陷的机制提供了新的见解。除了鉴定 Ube3a 底物外，人们还对 UBE3A 在神经元基因和蛋白质相互作用的表达谱中的综合作用有了新的认识。目前出现了一种发展模式，即 15 号染色体上 UBE3A 基因剂量改变了突触功能，功能不足导致安格曼综合征，而过表达则与经典自闭症症状相关。
