Mucosal glycosaminoglycan (GAG)

Mucosal glycosaminoglycans (GAGs) are long, unbranched polysaccharides consisting of repeating disaccharide units, typically found on the apical surface of epithelial cells and within the extracellular matrix of mucosal tissues (Kamhi et al., 2013). These molecules, which include heparan sulfate, chondroitin sulfate, and hyaluronic acid, often exist as part of larger proteoglycan complexes that serve as critical attachment receptors or co-receptors for a diverse array of pathogens, including SARS-CoV-2, herpes simplex virus, and various bacterial species (Clausen et al., 2020; Monzon et al., 2018). By providing an initial docking site, GAGs facilitate the concentration of pathogens on the cell surface, thereby enhancing their interaction with more specific entry receptors. Beyond their role in infection, mucosal GAGs are essential for maintaining the structural integrity and permeability of the epithelial barrier, particularly in the bladder and respiratory tract (Hurst et al., 2015). Therapeutic strategies targeting GAGs involve the use of GAG mimetics or competitive inhibitors, such as pentosan polysulfate or heparin derivatives, to either block pathogen entry or replenish a depleted mucosal lining in inflammatory conditions like interstitial cystitis (Hurst et al., 2015; FDA, 2023). However, because GAGs are involved in numerous physiological processes including anticoagulation and growth factor signaling, pharmacological modulation must be carefully managed to avoid systemic side effects (Sasisekharan et al., 2002).

Other names

GlycosaminoglycansMucosal GAG receptorsCell surface proteoglycansHeparan sulfate proteoglycansChondroitin sulfate proteoglycansEpithelial GAG layer

Competitive inhibition of pathogen binding to host cell surfaces and restoration of the protective epithelial glycan layer.