Terminal Complement Complex C5b-9 (C5b-9)

Complement activation with assembly of the terminal complement complex C5b-9, consisting of the C5b, C6, C7, C8, and C9 proteins, plays a significant role in the pathogenesis of a variety of CNS diseases, including MS . By forming pores in the plasma membrane, C5b-9 can cause cell death and also induce apoptosis .

However, OLG, like other nucleated cells, can survive limited C5b-9 complement attack through the protection provided by complement-inhibitory proteins and by elimination of membranes carrying C5b-9 complexes. C5b-9 at sublytic doses inhibits the mitochondrial pathway of apoptosis as well as caspase-3 activation induced in vitro by serum deprivation . This C5b-9 effect effectively rescues OLG from apoptosis and this process is mediated by Gi protein-dependent and G-mediated activation of the ERK1 and PI3K/Akt pathways .