Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-02

AUTHORS

May H. Han, Sun-Il Hwang, Dolly B. Roy, Deborah H. Lundgren, Jordan V. Price, Shalina S. Ousman, Guy Haskin Fernald, Bruce Gerlitz, William H. Robinson, Sergio E. Baranzini, Brian W. Grinnell, Cedric S. Raine, Raymond A. Sobel, David K. Han, Lawrence Steinman

ABSTRACT

Understanding the neuropathology of multiple sclerosis (MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser-capture microdissection and proteomics, proteins unique to three major types of MS lesions: acute plaque, chronic active plaque and chronic plaque. Comparative proteomic profiles identified tissue factor and protein C inhibitor within chronic active plaque samples, suggesting dysregulation of molecules associated with coagulation. In vivo administration of hirudin or recombinant activated protein C reduced disease severity in experimental autoimmune encephalomyelitis and suppressed Th1 and Th17 cytokines in astrocytes and immune cells. Administration of mutant forms of recombinant activated protein C showed that both its anticoagulant and its signalling functions were essential for optimal amelioration of experimental autoimmune encephalomyelitis. A proteomic approach illuminated potential therapeutic targets selective for specific pathological stages of MS and implicated participation of the coagulation cascade. More... »

PAGES

1076

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature06559

DOI

http://dx.doi.org/10.1038/nature06559

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024360978

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18278032


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