The Extracellular Matrix and Remyelination Strategies in Multiple Sclerosis

The role of ECM components in oligodendrocyte (OLG) remyelination. Multiple ECM components are inhibitors of OPC differentiation and migration, including CSPGs; (Lau et al., 2013; Pendleton et al., 2013), hyaluronan (HA; Sloane et al., 2010), TnC (Czopka et al., 2010), and fibrinogen (Petersen et al., 2017) via different signaling pathways. Laminin-2 (LM2) may not have significant effects on OPC differentiation, but it promotes myelin sheets formation in mature OLGs (Buttery and ffrench-Constant, 1999). TnR is also a pro-remyelinating component, and it improves OPC adhesion and differentiation (Pesheva et al., 1997). Aggregated fibronectin (aFn) in the highlighted paper is an inhibitor of OPC proliferation and OLG myelin formation (Qin et al., 2017), although the exact mechanisms are still unclear. Administration of GD1a (Qin et al., 2017), fluorasamine (Keough et al., 2016), and ancrod (Petersen et al., 2017) in animals can overcome the remyelination-inhibiting effects of aFn, CSPG, and fibrinogen, respectively. Thus, those compounds have translational potentials for remyelinating therapy. ACVR1, activin A receptor, Type I; PTPσ, protein tyrosine phosphatase sigma; ROCK, Rho-associated protein kinase.