Table 1.
Galectins during developmental myelination and upon de-and remyelination
| Galectin | Model | Main result | Mechanism | References |
|---|---|---|---|---|
| In vivo | ||||
| gal-1 | Lgals1−/− mice (C57Bl/6) | Less and more loosely wrapped myelinated axons | Controls myelin compaction and integrity | [156] |
| gal-1 |
Lysolecithin-induced demyelination (C57Bl/6 mice, treatment) |
Reduced demyelination and improved remyelination | Shifts microglia towards a regenerative phenotype, increases phagocytosis of myelin debris and OPC differentiation | [156] |
| gal-3 | Lgals3−/− mice (C57Bl/6) | Decreased percentage myelinated axons, myelin turns and g-ratio. Loosely wrapped and less smooth myelin | Required for proper production and organization of myelin | [123] |
| Lgals3−/− mice (129 Sv) | No effect on OPC differentiation upon development | [220] | ||
| gal-3 |
Cuprizone-induced demyelination (Lgals3−/− C57BL/6 mice) |
Decreased OPC differentiation, enhanced reactive astrogliosis, defective microglia activation and hypomyelination | Inability to upregulate the phagocytic receptor TREM-2b on microglia and decreased MMP-3 expression | [151, 221] |
|
Cuprizone-induced demyelination (Lgals3−/− 129Sv mice) | ||||
| Increased emigration of SVZ cells to demyelinated areas and no effect on OPC differentiation | Controls local inflammation in the SVZ and limits SVZ progenitor emigration | [220] | ||
| gal-4 | Cuprizone-induced demyelination (C57Bl/6 mice) | Re-expressed in axons and present in microglia/macrophages | Neuronal re-expression and secretion of gal-4 may inhibit OPC differentiation | [124, 179] |
| In vitro | ||||
| gal-1 | Astrocytes (primary cell culture F344/N Slc rats, treatment) | Induces differentiation and inhibits proliferation | Increases production of BDNF | [217] |
| gal-1 | Oligodendrocytes (primary cell culture, Wistar rats, treatment) | Low concentrations inhibit OPC differentiation | Upregulates MMP-2 activity in conditioned medium of immature oligodendrocytes that may cleave gal-3′s N-terminal tail | [123, 167] |
| High concentrations enhance OPC differentiation | May increase OPC viability upon cell cycle exit | |||
| gal-3 | Oligodendrocytes (primary cell culture, Wistar rats, treatment) | Promotes OPC differentiation | Gal-3′s N-terminal tail is cleaved by MMP-2 in OPCs, but not mature oligodendrocytes, gal-3 induces actin filament assembly and drives early branching of oligodendrocyte processes | [123, 167] |
| gal-3 | Microglia (Lgals3−/− C57BL/6 mice) | Microglia-conditioned medium with secreted gal-3 promotes OPC differentiation | Microglia-expressed gal-3 favors an anti-inflammatory phenotype | [123, 158] |
| gal-4 | Oligodendrocytes (primary cell culture, Wistar rats, treatment) | Inhibits OPC differentiation | Direct binding of gal-4 to the OPC (protein integrity with both CRDs and linker is required) | [124] |
| Oligodendrocytes (CG4 cells, primary cell culture) | Enhances MBP promotor activity | Involved in p27- and Sp1-mediated activation of MBP | [148] | |
| gal-4 | Cortical neurons (primary cell culture, co-culture with oligodendrocytes, Wistar rats) | Required for proper axon growth and elongation | Sorts and organizes transport of axonal L1 in a sulfatide-dependent manner | [125] |
| Gal-4 deposits on axons inhibit myelination | Possible role in recruitment of contactin-1 and correct targeting of nodes of Ranvier | [134] | ||
BDNF brain-derived neurotrophic factor, gal galectin, MMP matrix metalloproteinase, OPC oligodendrocyte progenitor cell, SVZ subventricular zone