% 0期刊文章%艾尔文Das %此人名叫她丹菲%桑德拉·卡多纳·%威廉·林奇% T做蛋白质能够导致海绵状神经退化引起Aggresomes在体外和在活的有机体内作为一个指示器的神经毒性机制?(P03.261) % D J神经病学20首页12% % P P03.261-P03.261 % V 78% N 1补充% X目的:探索神经变性aggresome形成的普遍性,我们调查是否aggresomes出现在两个海绵状神经退化模型、空泡形成的诱导神经干细胞(NSC)传播puromycin-N-acetyltransferase (PAC)或逆转录病毒信封(Env)发展中中枢神经系统(CNS)。背景几个人类神经退行性疾病的特点是存在的蛋白质称为aggresomes存款。以前的报告表明,PAC在某些培养细胞的表达导致蛋白质聚合。此外,从我们实验室在活体内研究表明,星形的表达PAC诱发Env引起的海绵状结构类似。本研究整理这些发现理解aggresomes是否蛋白质毒性体外和体内的指标。设计/方法:Aggresome标记被用来测定intracellar聚集在海拉和胶质细胞转染/转导与向量包含Env或PAC和绿色荧光蛋白(GFP),细胞识别标记。被处决的原位研究免疫染色在新生儿aggresomes小鼠移植nsc传播PAC或Env。病理上折射nsc转导与PAC显示表面Env担任控制。结果:没有发现aggresome形成针对神经毒性蛋白转染/转导;然而,这些蛋白质并引发意外下调GFP蛋白表达。 Moreover, brains engrafted with PAC-transduced NSCs precipitated focal spongiform neurodegeneration, thereby overcoming a previous restriction noted with Env. These NSCs differentiated into oligodendrocytes suggesting that PAC influenced their in vivo fate and capacity for inducing spongiosis.Conclusions: The present studies indicate that while spongiogenic proteins do not universally induce aggresome formation, they can alter cellular physiology by influencing endogenous protein expression and modifying cellular differentiation programs that result in neuronal dysregulation. Whether these activities are broadly applicable to other neurodegenerative diseases mediated by abnormal proteins remains to be investigated.Supported by: The American Academy of Neurology.Disclosure: Dr. Das has nothing to disclose. Dr. Dunphy has nothing to disclose. Dr. Cardona has nothing to disclose. Dr. Lynch has nothing to disclose.Tuesday, April 24 2012, 14:00 pm-18:30 pm %U

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