Proteomic profiling of the substantia nigra demonstrates CNDP2 overexpression in Parkinson's disease
| Autor: | Denis F. Hochstrasser, Eniko Veronika Kovari, Johannes Alexander Lobrinus, Jean-Charles Sanchez, Neftali Rodrigo, Virginie Licker, Pierre R. Burkhard, Natacha Turck, Mélanie Cote |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Dipeptidases Parkinson's disease Proteome Nerve Tissue Proteins/metabolism Biophysics Nerve Tissue Proteins Substantia nigra ddc:616.07 Biology Bioinformatics Proteomics Biochemistry Gene Expression Regulation Enzymologic Neuroglia/metabolism/pathology Pathogenesis ddc:616.89 Western blot Substantia Nigra/metabolism/pathology Immunohistochemistry/methods Dipeptidases/biosynthesis medicine Humans ddc:576 Aged Inflammation Aged 80 and over Inflammation/metabolism/pathology Dopaminergic Neurons/metabolism/pathology medicine.diagnostic_test Pars compacta Dopaminergic Neurons Neurodegeneration Parkinson Disease/metabolism/pathology Parkinson Disease medicine.disease Immunohistochemistry Substantia Nigra Oxidative Stress Female Dipeptidase 2 Neuroglia Neuroscience |
| Zdroj: | Journal of Proteomics, Vol. 75, No 15 (2012) pp. 4656-67 |
| ISSN: | 1874-3919 |
| DOI: | 10.1016/j.jprot.2012.02.032 |
| Popis: | Despite decades of intensive investigations, the precise sequence of molecular events and the specific proteins mediating the degenerative process underlying Parkinson's disease (PD) remain unraveled. Proteomic strategies may provide unbiased tools to identify novel candidates and explore original mechanisms involved in PD. Substantia nigra pars compacta (SN) tissue, whose degeneration is the hallmark of PD, was dissected from neuropathologically confirmed PD patients (n=3) and control subjects (n=3), before being submitted to a comparative 2-DE analysis. The present study revealed a subset of neuronal and/or glial proteins that appears to be deregulated in PD and likely to contribute to neurodegeneration. Observed alterations not only consolidate well accepted concepts surrounding PD pathogenesis such as oxidative stress and mitochondrial dysfunction but also point out to novel pathways. Among the latter, cytosolic non specific dipeptidase 2 (CNDP2), a relatively unknown protein not yet reported to be associated with PD pathogenesis, was shown to be increased in the SN of PD patients, as confirmed by Western blot. Immunohistochemical analyses demonstrated the presence of CNDP2 within the cytoplasm of SN dopaminergic neurons. Altogether, our findings support a key role of CNDP2 in PD neurodegeneration, by mechanisms that could involve oxidative stress, protein aggregation or inflammation. This article is part of a Special Issue entitled: Translational Proteomics. |
| Databáze: | OpenAIRE |
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