Schematic model of LPA-induced demyelination. The stimulation of LPA1 receptor first induces myelin to down-regulate compact myelin proteins, such as MBP, MPZ, and PMP22, and to loosen myelin structure. In addition, MAG is down-regulated and NOGO/p75 receptor complex (NgR/p75)-mediated activation of Rho-ROCK system is terminated. The latter mechanism results in inhibition of actin depolymerization, or sprouting. Degenerated Schwann cells (SCs) release neurotrophins, which in turn accelerate sprouting.