Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson's Disease.


Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
02 12 2020
Historique:
received: 15 09 2020
revised: 17 11 2020
accepted: 24 11 2020
entrez: 5 12 2020
pubmed: 6 12 2020
medline: 24 6 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33276480
pii: cells9122580
doi: 10.3390/cells9122580
pmc: PMC7761546
pii:
doi:

Substances chimiques

Melanins 0
Proteome 0
neuromelanin 0
thymidine kinase 2 EC 2.7.1.-
Thymidine Kinase EC 2.7.1.21
Metalloendopeptidases EC 3.4.24.-
neurolysin EC 3.4.24.16
Methionine-tRNA Ligase EC 6.1.1.10

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Sarah Plum (S)

Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany.

Britta Eggers (B)

Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany.
Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany.

Stefan Helling (S)

Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany.

Markus Stepath (M)

Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany.
Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany.

Carsten Theiss (C)

Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, 44780 Bochum, Germany.

Renata E P Leite (REP)

Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil.
Division of Geriatrics, LIM 66, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil.

Mariana Molina (M)

Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil.

Lea T Grinberg (LT)

Department of Pathology, LIM22, University of Sao Paulo Medical School, Sao Paulo 01246-903, Brazil.
Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA 94158, USA.

Peter Riederer (P)

Center of Mental Health, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Margarete-Höppel-Platz 1, 97080 Wuerzburg, Germany.
Psychiatry Department of Clinical Research, University of Southern Denmark Odense University Hospital, Winslows Vey 18, 5000 Odense, Denmark.

Manfred Gerlach (M)

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 (C)

Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany.
Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany.

Katrin Marcus (K)

Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801 Bochum, Germany.
Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr-University Bochum, 44801 Bochum, Germany.

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Classifications MeSH