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

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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.