RT期刊文章SR电子T1针对sphingosine-1-phosphate裂合酶是神经的神经元模型亨廷顿氏舞蹈症(P2.001)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP P2.001 VO 88是16补充A1艾琳Furr-Stimming A1安德烈T首页svetkov年2017 UL //www.ez-admanager.com/content/88/16_Supplement/P2.001.abstract AB目的:亨廷顿氏病是一种毁灭性的,渐进的神经退行性疾病,尽管进步在理解遗传和临床表现,仍然是在分子水平上了解甚少。自噬是一个重要的体内平衡机制,消除长期存在的蛋白质,蛋白质总量和受损的细胞器。其失调参与许多神经退行性疾病,如亨廷顿氏舞蹈病。我们的目标是识别小说潜在通道途径,如果修改,可以减缓或阻止疾病进展。背景:自噬是一种很有前途的目标削弱神经退化。我们寻找新的自噬通路在初级神经元和确定了胞质sphingosine-1-phosphate (S1P)通路神经元自噬的监管机构。S1P,生成的生物活性脂质鞘氨醇激酶1 (SK1)在细胞质中,参与细胞的生存。设计/方法:基于培养我们使用一个HD模型纹状体和皮质神经元,受影响最严重的高清,来源于胚胎大鼠。一种新型显微镜系统,自动成像和纵向分析,使我们能够追踪大军团个体神经元的一生。我们表示S1P-synthesizing和代谢酶在神经元,成像他们随着时间的推移,然后用于临床医学应用统计方法来确定酶增加突变杭丁顿蛋白的降解,促进神经元存活。结果:我们发现SK1提高通量通过自噬这S1P-metabolizing酶降低通量。在亨廷顿氏舞蹈症的神经元模型,药物抑制S1P-lyase保护神经元免受mutant-huntingtin-induced神经毒性。Conclusions: These results identify the S1P pathway as a novel regulator of neuronal autophagy and provide a new target for developing therapies for neurodegenerative disorders such as Huntington’s disease.Study Supported by: Hereditary Disease FoundationDisclosure: Dr. Furr-Stimming has received personal compensation for activities with Impax, Worrell Marketing Company, Teva, and Cynapsus for serving as an advisory board member. Dr. Furr-Stimming has received research support from Teva (previously Auspex) ARC HD, PPD, Adamas, and the CHDI Foundation. Dr. Tsvetkov has nothing to disclose.