Galectin-3: Roles in Neurodevelopment, Neuroinflammation, and Behavior

Abstract

There is a plethora of evidence to suggest that Galectin-3 plays an important role in normal functions of mammalian cells, as well as in different pathogenic conditions. This review highlights recent data published by researchers, including our own team, on roles of Galectin-3 in the nervous system. Here, we discuss the roles of Galectin-3 in brain development, its roles in glial cells, as well as the interactions of glial cells with other neural and invading cells in pathological conditions. Galectin-3 plays an important role in the pathogenesis of neuroinflammatory and neurodegenerative disorders, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. On the other hand, there is also evidence of the protective role of Galectin-3 due to its anti-apoptotic effect in target cells. Interestingly, genetic deletion of Galectin-3 affects behavioral patterns in maturing and adult mice. The results reviewed in this paper and recent development of highly specific inhibitors suggests that Galectin-3 may be an important therapeutic target in pathological conditions including the disorders of the central nervous system.

Galectin-3: a key player in microglia-mediated neuroinflammation and Alzheimer's disease

“…Galectins consist of evolutionarily highly conserved carbohydrate-recognition domains (CRDs) containing approximately 130 amino acid sequences that bind β-galactose in glycoconjugates [ 13 ]. In mammalian tissues, a total of 15 galectins have been identified to date, and they have been subdivided into three subtypes according to their structures [ 5 , 14 ]: the prototype galectins include the largest number of subgroups and contain a single CRD; the chimaera-type galectins contain a single CRD and an intrinsically disordered sequence at the N-terminal domain that promotes oligomerization; and the tandem-repeat type galectins consist of two CRD motifs (Fig.…”

Microglia‐derived galectin‐3 in neuroinflammation; a bittersweet ligand?

“…For example, a small molecule inhibitor, 33DFTG, has been shown to diminish pathological corneal neovascularization and fibrosis in experimental models. TD139 is another important Gal‐3 inhibitor in advanced phases of the clinical trial for lung fibrosis 8 . Gal‐3 inhibitors have been developed as new agents to offset lung fibrosis and hinder cancer metastasis.…”

“…Siew et al showed that plasma levels of Gal‐3 correlate with the severity of the Huntington's disease. Also, post‐mortem study of Huntington's disease brains revealed upregulation of Gal‐3 in the caudate‐putamen 8,17 …”

Biomarkers and Their Possible Functions in the Intestinal Microenvironment of Chagasic Megacolon: An Overview of the (Neuro)inflammatory Process

“…Finally, the authors concluded that gal-3 release in the central and peripheral 7 Journal of Immunology Research nervous systems would be directly related to intestinal neuronal death via toll-like receptor 4, an innate immunity receptor previously related to death induction in neurons [193]. Future studies need to focus on identifying gal-3 inhibitors for the control and treatment of CNS neuroinflammatory pathologies [194]. Thus, the use and search for these inhibitors may also represent alternatives for ENS-related diseases such as Chagasic megacolon.…”