The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. Currently approved disease-modifying treatment modalities are immunomodulatory or immunosuppressive. While the applied drugs reduce the frequency and severity of the attacks, their efficacy to regenerate myelin membranes and to halt disease progression is limited. To achieve such therapeutic aims, understanding biological mechanisms of remyelination and identifying factors that interfere with remyelination in MS can give respective directions. Such a perspective is given by the emerging functional profile of galectins. They form a family of tissue lectins, which are potent effectors in processes as diverse as adhesion, apoptosis, immune mediator release or migration. This review focuses on endogenous and exogenous roles of galectins in glial cells such as oligodendrocytes, astrocytes and microglia in the context of de-and (re)myelination and its dysregulation in MS. Evidence is arising for a cooperation among family members so that timed expression and/or secretion of galectins-1, -3 and -4 result in modifying developmental myelination, (neuro)inflammatory processes, de-and remyelination. Dissecting the mechanisms that underlie the distinct activities of galectins and identifying galectins as target or tool to modulate remyelination have the potential to contribute to the development of novel therapeutic strategies for MS.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Influence of protein (human galectin-3) design on aspects of lectin activity

“…Indeed, this is actually the case. With focus on the adhesion/growth-regulatory galectins, these multifunctional effectors are separated into three groups in vertebrates according to this criterion (Kasai and Hirabayashi 1996 ; Barondes 1997 ; Hirabayashi 1997 , 2018 ; Cooper 2002 ; Kaltner et al 2017a ; de Jong et al 2020 ).…”

What Cyto- and Histochemistry Can Do to Crack the Sugar Code

“…1 D) and its functional interplay with a tissue lectin (e.g. galectin-1) are emerging as molecular switch in autoimmunity, axonal repair and neuroblastoma growth regulation [ 11 , 28 , 49 ]. Illustrating the broadness of impact of this type of molecular pairing on cellular biology, an overview of the range of functions of glycan-lectin interplay is given in Table 2 .…”

Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes

“…Finally, the reported homo- and heterobivalency in the cross-linking assays explains well a role of Gal-4 in detergent-resistant membranes, and it may also underlie its specific role as suppressor for human colon cancer ( Michalak et al., 2017 , 2019 ; Rao and Rao, 2017 ; Rechreche et al., 1997 ; Satelli et al., 2011 ), as factor in oligodendrocyte differentiation and as inhibitor of myelination ( de Jong et al., 2018 , 2020 ; Díez-Revuelta et al., 2017 ; Stancic et al., 2012 ). Thus, the applied synthetic and supramolecular chemistry that led to detection of GDS bridging by sulfatide-Gal-4 pairing identifies a versatile means of letting sulfatide presence appear less enigmatic.…”