Analysis on aggregation formation by novel Lewy body component Siah-1 complementary to Parkin

据报道，突触蛋白1是路易小体的一个组成部分，路易小体是帕金森病的病理特征。在本研究中，我们建立了synphilin-1转基因小鼠作为帕金森病的模型动物进行分析。我们在朊蛋白启动子下产生了表达人synphilin-1的转基因小鼠。Synphilin-1在包括黑质在内的大脑神经元中广泛表达，而在黑质中没有观察到多巴胺神经元的大量丢失。在转基因小鼠脑内，synphilin-1蛋白多泛素化，部分不溶性。虽然shirpa修饰后的小鼠在行为学和形态学上没有显著差异，但与非转基因小鼠相比，转基因小鼠的旋转速度和步长都有所降低。Synphilin-1可能参与运动功能，其在中枢神经系统的积累可引起运动障碍。目前，我们正在通过高效液相色谱法测定转基因小鼠脑内多巴胺代谢，分析转基因小鼠出现运动障碍的机制。

Synphilin-1 is a protein reported as a component of Lewy bodies, which characterize Parkinson's disease pathologically. In this study, we established synphilin-1 transgenic mice to analyze as model animal of Parkinson's disease.We generated transgenic mice expressing human synphilin-1 under the prion protein promoter.Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed.In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble.Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments.We are now analyzing the mechanisms, by which transgenic mice showed motor impairment through the measurement of dopamine-metabolies in brain by HPLC.