Galectin-3 prospects as a therapeutic agent for multiple sclerosis

Abstract

Galectin-3 (Gal-3) in oligodendrocyte (OLG) differentiation:OLGs are the cells in charge of myelination in the central nervoussystem (CNS), allowing rapid conduction of the neuralaction potential and giving trophic support to axons. OLGs undergoa series of changes throughout their life cycle: first, uponneural stem cell commitment to the OLG lineage, cells referredto as OLG precursor cells (OPC) present a bipolar morphology,have proliferative and migratory capacity and express molecularmarkers like platelet-derived growth factor receptor alpha andneural/glial antigen 2; next, in an intermediate stage called pre-OLG, OLGs are more ramified and express CNPase, Olig1 andO4, among others; finally, cells develop into myelin formingcells which express molecular markers like myelin basic protein(MBP), adenomatous polyposis polyposis and proteolipidprotein (Franklin et al., 2017). Worth pointing out, the actincytoskeleton plays an important role in OLG maturation, as itevolves from pro-polymerization to pro-depolymerization dynamics,which allows axon ensheathing. These mechanisms arecontrolled in part by the relationship between MBP and actindisassembly proteins such as cofilin-1 and gelsolin. The latterare normally sequestered and inactivated by phosphatidylinositol4,5-bisphosphate present in the plasma membrane. WhenMBP is expressed in mature OLG, it competes with gelsolin andcofilin-1 for phosphatidylinositol 4,5-bisphosphate binding,displacing and hence activating them, to trigger the disassemblyof actin filaments.