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Title: | Identification of Protein Networks Involved in the Disease Course of Experimental Autoimmune Encephalomyelitis, an Animal Model of Multiple Sclerosis | Authors: | VANHEEL, Annelies DANIELS, Ruth Plaisance, Stephane BAETEN, Kurt HENDRIKS, Jerome Leprince, Pierre DUMONT, Debora ROBBEN, Johan BRONE, Bert STINISSEN, Piet NOBEN, Jean-Paul HELLINGS, Niels |
Issue Date: | 2012 | Publisher: | PUBLIC LIBRARY SCIENCE | Source: | PLOS ONE, 7 (4), e35544 | Abstract: | A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE), a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE) followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA). The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4), a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1), involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and networks that warrant further research to study their actual contribution to disease pathology. | Notes: | [Vanheel, Annelies; Daniels, Ruth; Baeten, Kurt; Hendriks, Jerome J. A.; Dumont, Debora; Brone, Bert; Stinissen, Piet; Noben, Jean-Paul; Hellings, Niels] Hasselt Univ, Biomed Res Inst, Hasselt, Belgium. [Vanheel, Annelies; Daniels, Ruth; Baeten, Kurt; Hendriks, Jerome J. A.; Dumont, Debora; Brone, Bert; Stinissen, Piet; Noben, Jean-Paul; Hellings, Niels] Transnat Univ Limburg, Sch Life Sci, Hasselt, Belgium. [Leprince, Pierre] Univ Liege, GIGA Neurosci, Liege, Belgium. [Plaisance, Stephane] VIB, Bioinformat Training & Serv Facil BITS, Ghent, Belgium. [Robben, Johan] Katholieke Univ Leuven, B-3001 Heverlee, Belgium. | Keywords: | Biology | Document URI: | http://hdl.handle.net/1942/13812 | ISSN: | 1932-6203 | e-ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0035544 | ISI #: | 000305347400060 | Rights: | 2012 Vanheel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2013 |
Appears in Collections: | Research publications |
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vanheel1.pdf | Published version | 1.05 MB | Adobe PDF | View/Open |
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