Proteomic Analysis of Striatum from MPTP-Treated Marmosets (Callithrix jacchus) with L-DOPA-Induced Dyskinesia of Differing Severity

Marmosets rendered parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with L-3,4-dihydroxyphenylalanine (L-DOPA) develop dyskinesia, but with differing degrees of severity. To provide insight into the molecular mechanisms responsible for the different level of dyskinesia to manifest in individual animals, proteins in striatum from MPTP-treated marmosets with different levels of L-DOPA-induced dyskinesia were separated by 2-dimensional (2-D) protein electrophoresis. Thirty-five differentially expressed proteins were identified by mass spectrometry and peptide mass fingerprinting, and comparative analysis found 10 were significantly increased and 3 had significantly reduced expression in animals with a high level of dyskinesia when compared to animals with a low incidence of dyskinesia. These proteins belonged to a range of functional classes, for example, molecular chaperones, metabolic enzymes and synaptic structural proteins. The findings of this study provide clues about the molecular mechanisms that cause dyskinesia to manifest and point towards potential novel targets for the development of therapeutic agents to prevent or treat established dyskinesia.