Galectin-3-mediated glial crosstalk drives oligodendrocyte differentiation and (re)myelination

THOMAS LAURA, PASQUINI LA

Frontiers in Cellullar Neuroscience

eCollection

Año: 2018

Galectin-3 (Gal-3) is the only chimeric protein in the galectin family. Gal-3 structurecomprises unusual tandem repeats of proline and glycine-rich short stretches boundto a carbohydrate-recognition domain (CRD). The present review summarizes Gal-3functions in the extracellular and intracellular space, its regulation and its internalizationand secretion, with a focus on the current knowledge of Gal-3 role in central nervoussystem (CNS) health and disease, particularly oligodendrocyte (OLG) differentiation,myelination and remyelination in experimental models of multiple sclerosis (MS).During myelination, microglia-expressed Gal-3 promotes OLG differentiation by bindingglycoconjugates present only on the cell surface of OLG precursor cells (OPC). Duringremyelination, microglia-expressed Gal-3 favors an M2 microglial phenotype, hencefostering myelin debris phagocytosis through TREM-2b phagocytic receptor and OLGdifferentiation. Gal-3 is necessary for myelin integrity and function, as evidenced bymyelin ultrastructural and behavioral studies from LGALS3􀀀=􀀀 mice. Mechanistically,Gal-3 enhances actin assembly and reduces Erk 1/2 activation, leading to early OLGbranching. Gal-3 later induces Akt activation and increases MBP expression, promotinggelsolin release and actin disassembly and thus regulating OLG final differentiation.Altogether, findings indicate that Gal-3 mediates the glial crosstalk driving OLGdifferentiation and (re)myelination and may be regarded as a target in the design offuture therapies for a variety of demyelinating diseases.