ABSTRACT
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.
Subject(s)
Dipeptidases/biosynthesis , Gene Expression Regulation, Enzymologic , Nerve Tissue Proteins/metabolism , Oxidative Stress , Parkinson Disease/metabolism , Substantia Nigra/metabolism , Aged , Aged, 80 and over , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Female , Humans , Immunohistochemistry/methods , Inflammation/metabolism , Inflammation/pathology , Male , Neuroglia/metabolism , Neuroglia/pathology , Parkinson Disease/pathology , Proteome , Substantia Nigra/pathologyABSTRACT
BACKGROUND: The detection of the presence of cerebrospinal fluid (CSF) in nasal secretions contaminated with blood and mucus remains a challenging clinical problem. METHODS: A prospective study was conducted from November 1998 to February 2002, including 42 patients. Samples (250 microL) of nasal secretions were analyzed by two-dimensional electrophoresis (2-DE). Plasma, mucus, and CSF were identified by specific proteins markers corresponding to characteristic trains of spots. Intrathecal injection of fluorescein followed by the detection of fluorescein on endoscopic examination of the nasal cavities was considered a positive reference for CSF rhinorrhea. RESULTS: In all cases of positive fluorescein test, we unambiguously observed the presence of several specific CSF markers onto the 2-DE gels. Conversely, all negative fluorescein tests were associated with the absence of CSF-specific spots. CONCLUSIONS: Two-DE analyses of biologic fluids of nasal origin should be considered as a reliable diagnostic tool in case of suspicion of CSF leak.
