Gel-forming respiratory mucin disulfide bonds

Gel-forming respiratory mucins, primarily MUC5AC and MUC5B, are high-molecular-weight glycoproteins that constitute the structural scaffold of the airway mucus gel (Bonser & Erle, 2017). These mucins polymerize through the formation of intermolecular disulfide bonds between their N-terminal and C-terminal cysteine-rich domains, creating a complex, viscoelastic network (Thornton et al., 2008). In pathological conditions such as cystic fibrosis, COPD, and severe asthma, the density of these disulfide cross-links increases, leading to mucus hyper-viscosity and impaired mucociliary clearance (Fahy & Dickey, 2010). Reducing agents, such as N-acetylcysteine and newer thiol-based mucolytics like P-2119, target these disulfide bonds to break the polymers into smaller, less viscous fragments (Ehre et al., 2019). This therapeutic intervention aims to facilitate mucus clearance and improve airflow in patients with obstructive lung diseases (StatPearls, 2023). Furthermore, the development of next-generation mucolytics focuses on increasing the potency and duration of disulfide bond reduction to overcome the limitations of traditional therapies (Ehre et al., 2019).

Other names

Mucin disulfide bridgesMucin cross-linksCysteine-mediated mucin polymers

Reduction of intermolecular disulfide bonds between mucin monomers, leading to depolymerization and decreased mucus viscosity.