Mucin disulfide networks in airway mucus

Mucin disulfide networks are the fundamental structural framework of the airway mucus gel, primarily composed of the large, secreted polymeric glycoproteins MUC5AC and MUC5B [Fahy, 2010]. These mucins undergo extensive post-translational modification and form massive, high-molecular-weight oligomers through disulfide bond formation between cysteine-rich D-domains at their N- and C-termini [Thornton, 2008]. This cross-linked network is essential for the viscoelastic properties of mucus, which allow it to trap inhaled particles and be transported out of the lungs by ciliary action [Bonser, 2017]. In pathological states like cystic fibrosis, COPD, and severe asthma, the density of these disulfide cross-links increases or the mucus becomes dehydrated, resulting in stagnant, thick mucus that obstructs the airways and promotes infection [Bonser, 2017]. Therapeutic intervention typically utilizes mucolytic agents, such as N-acetylcysteine, which contain free thiol groups that participate in thiol-disulfide exchange reactions to break the mucin polymers into smaller, less viscous fragments [Yuan, 2015]. By reducing the connectivity of the disulfide network, these drugs facilitate the clearance of obstructive mucus and improve lung function in patients with chronic respiratory diseases [Fahy, 2010].

Other names

Mucin polymersDisulfide-linked mucin oligomersAirway mucus gelMUC5AC/MUC5B networks

Reduction of intermolecular disulfide bonds via thiol-disulfide exchange, leading to the fragmentation of mucin polymers and reduction of mucus viscoelasticity.