Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease
1
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany
2
Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany
3
Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44780 Bochum, Germany
4
Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil
5
Division of Geriatrics, LIM 66, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil
6
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA 94158, USA
7
Center of Mental Health, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Margarete-Höppel-Platz 1, 97080 Wuerzburg, Germany
8
Psychiatry Department of Clinical Research, University of Southern Denmark Odense University Hospital, Winslows Vey 18, 5000 Odense, Denmark
9
Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, University of Wuerzburg, 97080 Wuerzburg, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Cells 2020, 9(12), 2580; https://doi.org/10.3390/cells9122580
Received: 15 September 2020 / Revised: 17 November 2020 / Accepted: 24 November 2020 / Published: 2 December 2020
(This article belongs to the Special Issue Synaptic Dysfunction in Health and Disease)
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.