Galectins: structure, function and therapeutic potential

Abstract

Galectins are a family of animal lectins that bind beta-galactosides. Outside the cell, galectins bind to cell-surface and extracellular matrix glycans and thereby affect a variety of cellular processes. However, galectins are also detectable in the cytosol and nucleus, and may influence cellular functions such as intracellular signalling pathways through protein-protein interactions with other cytoplasmic and nuclear proteins. Current research indicates that galectins play important roles in diverse physiological and pathological processes, including immune and inflammatory responses, tumour development and progression, neural degeneration, atherosclerosis, diabetes, and wound repair. Some of these have been discovered or confirmed by using genetically engineered mice deficient in a particular galectin. Thus, galectins may be a therapeutic target or employed as therapeutic agents for inflammatory diseases, cancers and several other diseases.

Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8

“…4a; Supplementary Fig. S6) 19,20,24 . However, our complex structure showed that NDP52 only binds to the C-CRD.…”

“…There is no apparent functional relevance of the NAD association with the N-CRD of GAL8, but this finding needs further investigation. Indeed, several galectins are recognized as potential targets for both anti-cancer and antiinflammatory drugs 24,[30][31][32][33] . As GAL8 is involved in many cellular processes, including cell adhesion, apoptosis, innate immunity and bacterial clearance 12,16,24,34 , it would be useful to develop a small compound to modulate the function of GAL8.…”

Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis

“…35 In contrast, galectin-3 can act in a dual fashion; while extracellular galectin-3 has apoptotic activity, intracellular galectin-3 can protect cells from apoptosis. 10,23 In the present study, we monitored the expression of galectin-1 and galectin-3 in the ankle joint during disease progression in rats with CIA.…”

Presence of galectin-1 in the epidermal and dermal thickening of keloid tissues

“…Of particular interest, is that increased epidermal thickness not attributable to hyperproliferation, but possibly caused by abnormal terminal differentiation of keratinocytes that involves an increased expression of involucrin in the spinous and granular layers, has been recently reported in keloid scars [18]. Regarding the expression of Gal-1 in normal and pathological tissues, some studies highlighted that Gal-1 is detected in the cell nucleus, cytoplasm and intracellular and extracellular sides of cell membrane regulating cell growth, cellcell and cell-matrix adhesion, cell proliferation, differentiation, migration and survival [31][32][33][34], and that its expression might be induced by elevated levels of pro-inflammatory cytokines and growth factors [27,33,50,51]. Therefore, it is possible that Gal-1 contributes to the abnormal stratification and differentiation of keratinocytes in keloid tissues by upregulation of involucrin expression, and that a differential regulation of Gal-1 and Gal-3 expression would be occurring during the progression of keloid considering that Gal-1 was reduced or absent in normal epidermis and was present in the epidermal thickening of keloids, while Gal-3 appears gradually in normal epidermis and absent or decreased in the epidermal thickening of some skin lesions such as psoriasis, basal cellular carcinoma and lichen planus [37,52,53].…”

“…It has been detected in the cell nucleus, cytoplasm and intracellular and extracellular sides of cell membrane, and can be secreted and found in the extracellular space [31]. Gal-1, like others galectins, participates in signaling pathways and regulates a variety of biological responses including cell growth, cell-cell and cell-matrix adhesion, cell differentiation, migration, proliferation and survival [31][32][33][34] and plays a critical role in inflammation, angiogenesis, and tumor development and progression [27,33,35,36]. In human skin, Gal-1 has been implicated in psoriasis [37,38] and malignant lesions including cutaneous cancer [39], mycosis fungoides [40,41], and melanoma [42], and scarce studies have shown that the expression of Gal-1 is upregulated in keloid tissue [43].…”