Galectin-1 in myelin repair

Galectin-1 (Gal-1) is a member of a highly conserved family of animal lectins which binds to the common disaccharide [Galβ(1-4)-GlcNAc] on both Nand O-glycans decorating cell surface glycoconjugates. Current evidence supports a role for Gal-1 in the pathophysiology of multiple sclerosis (MS), one of the most prevalent chronic inflammatory diseases, as approximately one third of MS patients generate high titres of anti-Gal-1 antibodies. Four different lesion types have been described in MS: pattern-1 and -2 lesions are thought to be mediated by the autoimmune response, while pattern-3 and -4 lesions are considered primary oligodendropathy. The first two types are experimentally simulated in mice by experimental autoimmune encephalomyelitis (EAE), while the second two are mimicked by toxic models such as cuprizone (CPZ) or lysolecithin (LPC) administration. Studies in EAE models have demonstrated that Gal-1 is highly expressed in the acute phase of the disease and that its deficiency leads to severe inflammation-induced neurodegeneration [1]. Regarding its mechanism of action, Gal-1 binds to core 2 O-glycans on CD45 and induces its retention on the microglial surface, increasing CD45 phosphatase activity and inhibitory function. Adoptive transfer of Gal-1-secreting astrocytes or administration of recombinant Gal-1 at disease onset ‒after inflammatory cells have entered the CNS‒ attenuates EAE severity and reduces microglial activation [1]. However, these studies using the EAE model, in which damage is the consequence of an immunological attack to myelin, have failed in determining whether Gal-1 effects are due to damage suppression or response modulation against demyelination. On the other hand, Rinaldi et al. [2] have shown that, upon focal LPC-induced demyelination, Gal1 treatment induces both a significant decrease in demyelinated areas and more efficient remyelination, as observed when Gal-1 is administered immediately after or 4 days after LPC, respectively. This effect is accompanied by an attenuated oligodendroglial progenitor, microglial and astroglial response, which also reflects lesser myelin Editorial: Neuroscience