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, Stéphane
Baeten, Kurt
Hendriks, Jerome J.A.
Leprince, Pierre
Dumont, Debora
Robben, Johan
Brône, Bert
Stinissen, Piet
Noben, Jean-Paul
Hellings, Niels #
Issue Date: Apr-2012
Publisher: Public Library of Sciene
Series Title: PLoS One
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.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry, Molecular and Structural Biology Section
× corresponding author
# (joint) last author

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