Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease
Sarah Plum,
Britta Eggers,
Stefan Helling,
Markus Stepath,
Carsten Theiss,
Renata E. P. Leite,
Mariana Molina,
Lea T. Grinberg,
Peter Riederer,
Manfred Gerlach,
Caroline May,
Katrin Marcus
Affiliations
Sarah Plum
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
Britta Eggers
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
Stefan Helling
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
Markus Stepath
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
Carsten Theiss
Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44780 Bochum, Germany
Renata E. P. Leite
Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil
Mariana Molina
Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil
Lea T. Grinberg
Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil
Peter Riederer
Center of Mental Health, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Margarete-Höppel-Platz 1, 97080 Wuerzburg, Germany
Manfred Gerlach
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, University of Wuerzburg, 97080 Wuerzburg, Germany
Caroline May
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
Katrin Marcus
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
The pathological hallmark of Parkinson’s disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.
