RT期刊文章SR电子T1的子集轴突和突触基因表达水平改变了/拼接SMA-MNs港口与SMN / SYNCRIP复杂交互的一个共同的主题(S29.005)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP S29.005 VO 90 15补充A1 Federica Rizzo A1莫妮卡Nizzardo A1 Shikha Vashisht A1瓦伦蒂娜首页梅尔齐A1艾琳Faravelli A1塞布丽娜Salani A1莫妮卡Bucchia A1 A1事务Michela塔亚纳Andreina Bordoni A1 Nereo Bresolin A1 Uberto Pozzoli A1 Giacomo Comi A1普螺旋器年2018 UL //www.ez-admanager.com/content/90/15_Supplement/S29.005.abstract AB目的:识别小说分子治疗靶点在脊髓性肌萎缩(SMA)。背景:SMA是一种遗传性运动神经元(MN)疾病引起的SMN1基因突变。确切的致病机制和选择性MNs脆弱性的原因仍然没有被完全了解。SMN已经证明拥有一个重要角色在RNA拼接,尽管SMN缺陷之间的关系的深入分析,特定的基因表达/拼接变化和共同主题的存在改变了基因的序列仍然缺乏。设计/方法:我们从诱导多能干细胞生成的MNs(万能)SMA患者和健康对照组。我们在2000年Illumina公司HiSeq RNA进行测序。我们有针对性的40 m集群平均每样例。候选人记录/蛋白质与qPCR验证和免疫印迹。我们寻找共同的RNA序列(即四聚物分布),可以预测沉默或增强的外显子。功能的评估目标基因是由overexpressing或者沉默iPSC-derived MNs慢病毒载体。结果:我们深RNA进行测序和生物信息学分析MNs来自万能的SMA患者和健康者。我们发现SMA-specific分子MNs的变化,包括在轴突和突触基因异常如Neurexin和Synaptotagmin基因家族。 Motif enrichment analysis of differentially expressed/spliced genes in SMA-MNs revealed the presence of a common Motif-7, which is the target of SYNCRIP protein. Interestingly, SYNCRIP interacts only with SMN full-length and binds several of these key MN genes suggesting that the impairment of SMN/SYNCRIP interaction in SMA can be responsible for the observed gene expression/splicing misregulation. Overexpression of SYNCRIP in human SMA iPSCs-derived lines improved MN survival and increased motor axon length, restoring identified candidate downstream targets of RNA-processing dysfunction induced by SMN deficiency.Conclusions: These findings demonstrated that SMN/SYNCRIP complex through motif-7 might account for selective MN degeneration and represent a potential therapeutic target.Study Supported by: Cariplo grant (2012–0513) and JPND (DAMNPATHS) to SC.Disclosure: Dr. Rizzo has nothing to disclose. Dr. Nizzardo has nothing to disclose. Dr. Vashisht has nothing to disclose. Dr. Melzi has nothing to disclose. Dr. Faravelli has nothing to disclose. Dr. Salani has nothing to disclose. Dr. Bucchia has nothing to disclose. Dr. Taiana has nothing to disclose. Dr. Bordoni has nothing to disclose. Dr. Bresolin has nothing to disclose. Dr. Pozzoli has nothing to disclose. Dr. Comi has nothing to disclose. Dr. Corti has nothing to disclose.