Fig. 2

Molecular mechanism of remyelination in CNS. In response to the CNS injury to myelinate axons, remyelination is initiated with oligodendrocyte progenitor cells (OPCs) recruitment and activation to the lesion site. Then followed by OPCs proliferation, differentiation, and maturation to mature oligodendrocyte for myelin sheath formation. CNS injuries often along with the disruption of blood-brain barrier (BBB) in the lesion site. Systemic factors leaked from BBB contribute to the remyelination through promoting OPCs proliferation, differentiation, and maturation. Pancreas-derived FGF21 and adipose tissue-derived leptin promotes OPCs proliferation; skeletal muscle-derived prostacyclin, and lung, muscle, adipose tissue-derived apelin are responsible for the oligodendrocyte differentiation; spleen-derived transforming growth factor-β1 in serum induces the oligodendrocyte maturation. In contrast, fibrinogen disrupts OPCs differentiation and myelination upon BBB disruption. Therapeutic depletion of fibrinogen will be benefit for remyelination. OPCs, similar to other adult stem cell, undergo a functional decline with ageing. The ability of OPCs to self-renew and to differentiate is diminished. Also, the efficiency of oligodendrocyte differentiation is declined with age. In particular, the expression of apelin receptor (APJ) in oligodendrocytes is decreased and result in an insufficient remyelination. Alternatively, activation of APJ promotes the remyelination both in aged mice and toxin-induced EAE. Therefore, activation of apelin/APJ signaling restores the function of oligodendrocyte for differentiation and thereby enhance its capacity for remyelination