Overview of emerging therapies for demyelinating diseases

Table 1 Summary of different cell types and their function during remyelination and demyelination

Cell type	Role during remyelination		Roles during demyelination
Microglial cell: M2 phenotype	Promotes repair and efficient removal of debris to enhance remyelination by expressing the TREM-2 receptor on the cell surface	Microglial cell: M1 phenotype	Produces pro-inflammatory cytokines, further activating demyelination by recruiting phagocytes to the area as well as generating reactive oxygen species
Oligodendrocyte progenitor cell	Precursor cell type found in the central nervous system that have the potential to differentiate into oligodendrocytes
Oligodendrocyte	Cell type in the central nervous system that produces myelin
Astrocytes	Generate a protein network to localize inflammation and sparing tissue		Can form glial scars, impeding OPC entry. Secretes TNF-α, which further promotes phagocytosis and demyelination

OPC: Oligodendrocyte precursor cell; TNF-α: Tumor necrosis factor-alpha.

Table 2 Summary of important chemokines during demyelination and remyelination

Pro-inflammatory (demyelination) chemokines	Cell type that produces chemokine	Chemokine function	Anti-inflammatory (remyelination) chemokines	Cell type that produces chemokine	Chemokine function
TNF-α	Astrocytes	Promotes demyelination and oligodendrocyte pathology	TGF-β	Microglia (M2)	Promotes differentiation of different cell types during repair
(iNOS+)	Microglia (M1)	Promotes the M1 phenotype, a pro-inflammatory state and induces phagocytosis	Insulin-like growth factor-1	1 Astrocytes; 2 Microglia (M2)	Regenerative role that promotes remyelination by promoting differentiation of different cell types such as oligodendrocytes
TREM-2	Microglia (M2)	Cell surface receptor that clears myelin debris and promotes phagocytosis	Fibroblast growth factor 2	1 Astrocytes; 2 Microglia (M2)	Regenerative role that promotes remyelination by promoting differentiation of different cell types such as oligodendrocytes
			Arg-1+	Microglia (M2)	Promotes the M2 phenotype, an anti-inflammatory state

TNF-α: Tumor necrosis factor-alpha; TGF-β: Transforming growth factor beta.