Abstract
Galectin-3 (Gal-3), the only chimera-like galectin, has three structural domains: (a) the NH2 terminal domain containing serine phosphorylation, important for nuclear localization, secretion and oligomerization; (b) a sequence susceptible to metalloprotease (MMP) cleavage; and (c) a C-terminal domain containing the carbohydrate recognition domain (CRD) and an anti-death motif.
Highlights
Galectins (Gals) are a group of 15 proteins characterized by a highly conserved carbohydrate-recognition domain (CRD) and made up of approximately 130 amino-acids which bind β-galactose in glycoconjugates
Gal-3 is essential for microglial polarization following central nervous system (CNS) injury, with different effects on different injuries probably responding to time- and contextdependent factors [98]
Gal-3 involvement in alternative microglial polarization induced by IL-4, as that taking place in macrophages [103], may explain the effect of Gal-3 on cell commitment toward the oligodendroglial lineage, as IL-4-activated microglia favor oligodendrogenesis through a mechanism mediated by IGF-I, while IFN-gamma-activated microglia favor neurogenesis [104]
Summary
Galectins (Gals) are a group of 15 proteins characterized by a highly conserved carbohydrate-recognition domain (CRD) and made up of approximately 130 amino-acids which bind β-galactose in glycoconjugates. These studies revealed an increase in Akt activation and β-catenin, MBP and gelsolin levels, together with a decrease in Erk1/2 activation [29] Along these lines, recent reports have shown that the Akt/mTORC and Erk1/2 pathways play independent and cooperative roles in OLG differentiation along development and adulthood both in vitro and in vivo [30], and that Erk 1/2 inhibition favors OLG generation and recovery in demyelinating diseases [31]. Signaling pathways interacting with rGal-3 included nucleoside diphosphate kinase A (NME1), whose function is to inhibit OPC differentiation [42] and, strikingly, many subunits of the proteasome, which is known to degrade β-catenin, profilin 1, gelsolin, and MBP in OLG [43,44,45] This suggests an inhibitory relationship between rGal-3 and these subunits of the proteasome, which may explain the increase in the levels of several proteins found upon rGal-3 treatment. WT mice show an increase in MMP-3 expression and a decrease in CD45, TNFα, and TREM-2b+ cells during remyelination, while LGALS-/-mice exhibit no changes either in demyelination or remyelination [97]
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