FIGURE 10.

Inflammatory proteolytic pathway to MS. Phase 1, persistent inflammation caused by viral and bacterial infections and other related factors up-regulates PCs (furin and PC2), MMP-25, and BG21 (up arrows) in the stimulated antigen-presenting macrophages. Autoactivated PCs activate MMP-25, which then cleaves BG21 (the down arrows). The immunogenic fragments of the MBP portion of BG21 are presented in the major histocompatibility complex on the cell surface leading to the activation of the specific populations of the autoimmune T cells. Phase 2, if the brain barrier is not intact, the activated T cells home to the brain, attack the neuronal MBP, and cause inflammation leading to the macrophage infiltration and the follow-up up-regulation of the activity of multiple MMP types, many of which contribute to the further destruction of MBP and to the local demyelination causing plaque formation.