Esclerose múltipla: análise proteica das lesões

Vol 451 | 28 February 2008 | doi:10.1038/nature06559

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Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets
May H. Han1*, Sun-Il Hwang3*, Dolly B. Roy4*, Deborah H. Lundgren3, Jordan V. Price1, Shalina S. Ousman1,
Guy Haskin Fernald5, Bruce Gerlitz6, William H. Robinson2, Sergio E. Baranzini5, Brian W. Grinnell6, Cedric S. Raine7,
Raymond A. Sobel8, David K. Han3 & Lawrence Steinman1
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.
Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) with diverse clinical presentations and heterogeneous histopathological features. Understanding the neuropathology of MS is essential to develop improved therapies.
MS lesions or ‘plaques’ in the CNS white matter have distinct histological and immunocytological characteristics depending on