Mucin disulfide networks

Mucin disulfide networks are the primary structural components of the airway mucus gel, consisting of large, gel-forming glycoproteins, specifically MUC5AC and MUC5B (Bonser et al., 2016, JCI Insight). These mucins form high-molecular-weight polymers through intermolecular disulfide bonds between their cysteine-rich domains, which are essential for the viscoelastic properties of mucus (Fahy & Dickey, 2010, NEJM). In healthy individuals, these networks facilitate mucociliary clearance and provide a protective barrier against pathogens; however, in chronic inflammatory airway diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the networks become excessively cross-linked and dehydrated (Yuan et al., 2015, JCI). This leads to the formation of thick, stagnant mucus plugs that obstruct airflow and promote infection. Therapeutic agents known as mucolytics, such as N-acetylcysteine (NAC), target these networks by acting as reducing agents that cleave the disulfide bonds (DrugBank DB06151). This chemical reduction breaks the mucin polymers into smaller subunits, significantly decreasing mucus viscosity and improving the patient's ability to clear secretions via coughing or ciliary action. Beyond mucins, other disulfide-containing proteins like albumin can also be incorporated into these pathological networks, further increasing their tenacity.

Other names

Airway mucus gelMucin polymersGel-forming mucinsMUC5AC-MUC5B complexMucin disulfide-containing proteinsMucin disulfide networks and other disulfide-containing proteins in airway secretions

Reduction of intermolecular disulfide bonds to depolymerize mucin networks and decrease mucus viscosity.