Parkinson's disease(PD)has been viewed as a disease characterized by loss of the nigrostriatal dopaminergic projection and presence of Lewy bodies,whose major component is α-Synuclein(a-Syn)[1].However,the number of striatal dopaminergic neurons is increased in patients with PD.It may be compensate for loss of nigral input for PD patients.The exact mechanism of why new dopaminergic neurons in PD' striatum is not elucidated yet.In this work,we try to discovery differential proteins about the new dopaminergic neurons between PD model and control.Experimentally,A30P mutant α-Synuclein(a-Syn)transgenic mice model was established,rotational behavior was performed and the 11-month a-Syn model showed strong PD symptoms[2].Comparative O18-labeling quantitative proteomic strategy was used to detect the differentially expressed proteins in mice striatum.The proteins in striatum were digested by trypsin and then the peptides were separated by Strong Cation Ion Exchange(SCX)Chromatography as the first dimension.Each SCX fraction was subjected into High Performance Liquid Chromatography,as the second dimension,coupled with ESI-QTOF triplicate.Preliminary results showed that 21 proteins were up-regulated and 183 proteins were down-regulated.The neurofilament light/medium/heavy chain polypeptide,which forms the major intermediate filament in neurons and axons,tubulin,actin,myelin proteolipid protein and microtubule-associated protein were down-regulated.These results indicated that cytoskeleton is affected in PD model.Moreover,Mitochondrial Complex Ⅰ,Ⅲ,and Ⅴ were also downregulated.While,malate dehydrogenase,NADP-dependent malic enzyme and aldehyde dehydrogenase were up-regulated and antioxidant protein including DJ-1 protein,Glutathione S –transferase,superoxide dismutase [Mn],which act as the defense mechanism against oxidative damage,are found up-regulated.Our study revealed that PD influences the expression of metabolic proteins in striatum resulting in discrepancies in the energy budget of the neurons.In addition,synapsin-1,syntaxin-binding protein 1,adaptor protein complex 2,clathrin heavy chain 1,syntaxin-1B,associated with synaptic vesicle and transport,were found down-regulated.It may provide evidence for dopamine synaptic dysfunction prior to loss of striatal dopamine.