Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson’s disease

Parkinson´s disease (PD) feature a progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Additionally, numerous studies indicate an altered synaptic function during the course of PD. In order to characterize the proteome of synaptosomes isolated from the substantia nigra and to gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was conducted. Synaptosomes were isolated from substantia nigra tissue of control subjects free of pathology (N = 5) and individuals at advanced PD stages (N = 5) by density gradient centrifugation and further analyzed by mass spectrometry. 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome includes all proteins expressed within the synapses without regards to data analysis software, gender, age or disease. The CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, mitochondrial,, Neurolysin, and Methionine-tRNA ligase, mitochondrial (MARS2)) were underrepresented suggesting an alteration in mitochondrial translation in PD synaptosomes.