Table 1.

List of possible drugs to modulate microglia towards a regenerative phenotype in multiple sclerosis.

Modulators of Microglial Phagocytic Phenotype
Drug	Mechanism	Reference
Docosahexaenoic acid and Eicosapentaenoic acid	Enhance myelin phagocytosis by microglia	[87]
Endocannabinoid 2-AG	Upregulates the expression levels of phagocytosis associated genes and promotes microglial myelin uptake	[92]
Pseudoginsenoside-F11	Accelerates CR3-dependent myelin phagocytosis by microglial cells	[93]
rHIgM22	Binds to myelin debris and facilitates their internalization by microglia	[88]
Ursolic acid *	Agonist of PPARγ signaling, which upregulates the expression of CD36 receptor, involved in the internalization of Aβ and lipids	[97]
Galantamine *	Favors microglial Aβ internalization	[99]
Modulators of Microglial Lipid Metabolism
Drug	Mechanism	Reference
LBH589 # and Vorinostat #	Both HDAC inhibitors that increase NPC expression in fibroblasts, promoting the release of cholesterol from lysosomes	[124,125]
FTY720	HDAC inhibitor that also promotes lipid efflux from human primary macrophage through the overexpression of both NPC proteins and ABC transporters	[126,127]
DMHCA, GW3965, Wy14643, Rosiglitazone and Troglitazone	Activators of LXR/RXR heterodimeric transcription factor which upregulates ABC transporters thus also promoting cholesterol/lipid exit from macrophages	[118,119,120,121,122,123]

* Both Ursolic acid and Galantamine affect cell phagocytosis, for what we highlight them as good candidates to modulate myelin phagocytosis. ^# The effect of LBH589 and Vorinostat on the expression of NPC proteins in microglia is unknown. Further studies are needed to evaluate the potential of these molecules on microglial lipid metabolism. CR3: Complement receptor 3; PPAR: Peroxisome proliferator-activated receptor; Aβ: Amyloid-β; HDAC: Histone deacetylase; NPC: Niemann-Pick type disease C; ABC: ATP-binding cassette; LXR: liver X receptor; RXR: Retinoid X receptor.