Airway mucin disulfide bonds

Airway mucin disulfide bonds are the critical covalent linkages that facilitate the polymerization of secreted mucins, primarily MUC5AC and MUC5B, into a complex gel-like network [1]. These bonds form between cysteine-rich von Willebrand factor (vWF)-like domains at the N- and C-termini of mucin monomers, determining the rheological properties and viscoelasticity of airway mucus [2]. In pathological conditions such as cystic fibrosis, COPD, and severe asthma, the density of these disulfide cross-links increases, often exacerbated by oxidative stress and dehydration, resulting in thick, stagnant mucus that obstructs the airways [3]. Therapeutic strategies target these bonds using reducing agents, known as mucolytics, which contain free thiol groups that undergo disulfide exchange reactions with the mucin polymers [4]. By breaking these covalent bridges, the drugs reduce the molecular weight of the mucin network, lowering mucus viscosity and enhancing the effectiveness of cough and mucociliary clearance [5].

Other names

Mucin disulfide bridgesMucin cross-linksInter-mucin disulfide bondsPolymeric mucin linkages

Reduction of intermolecular disulfide bonds via thiol-disulfide exchange to fragment mucin polymers and decrease mucus viscosity.