Table 1.

Regulators of white matter damage and OPC regeneration, and their documented effects.

Pathway/protein	Mechanism/activity	Outcome/effect	Reference
Activity-dependent signals
ATP	A1 adenosine receptor on oligodendrocytes	↑ OPC differentiation, maturation and migration	Othman et al., 2003 Stevens et al., 2002
cAMP	MEK-ERK pathway (?)	↑ T remyelination ↑ OPC maturation	Malone et al., 2013 Sun et al., 2012
ECM-related proteins
CSPGs	Inhibitory GAG chains	↓ OPC differentiation, maturation and migration	Lau et al., 2012 Sherman and Back, 2008
hyaluronan	Digested by Hyaluronidase CD44, TLR2 signaling	↓ OPC differentiation, maturation ↑ progressive demyelination	Back et al., 2005 Sloane et al., 2010
MMPs	Degradation of MBP, MAG and ECM proteins	↑ T demyelination	Walker and Rosenberg, 2010
Wnt signaling
Wnt/β-catenin	Nuclear β-catenin/tcf/LEF complex	↓ OPC differentiation, maturation	Fancy et al., 2009 Feigenson et al., 2009
Axin2	β-catenin degradation	↑ remyelination	Fancy et al., 2011
APC	β-catenin regulation cytoskeletal regulation	↑ OPC proliferation, differentiation	Lang et al., 2013
HIF	Autocrine Wnt7a/7b signaling	↓ developmental myelination ↑ White matter angiogenesis	Yuen et al., 2014
Sox17	β-catenin degradation	↑ oligodendrocyte differentiation	Ming et al., 2013
Nogo related proteins
NogoA/NgR	RhoA(?), Rho kinase ROCK (?)	↓ remyelination, OPC recruitment	Pourabdolhossein et al., 2014 Niederost et al., 2002
LINGO-1	self-association, homophilic intercellular interactions	↓ OPC differentiation, maturation ↓ remyelination	Mi et al., 2009 Jepson et al., 2012
Additional regulators
Shh	Induces Olig1 and Olig2 expression	↑ oligodendrogenesis ↑ OPC maturation, differentiation	Harsan et al., 2008 Ferent et al., 2013
Netrin-1	Signaling through Dcc, RhoA inhibition	↑ OPC proliferation, differentiation ↑ remyelination	Rajasekharan et al., 2009 He et al., 2013
LIF	Akt signaling, antioxidation	↓ white matter injury, infarct volume	Rowe et al., 2014