Citation

Kelly-Robinson GA, Reihill JA, Lundy FT, McGarvey LP, Lockhart JC, Litherland GJ, Thornbury KD, Martin SL. Int. J. Mol. Sci. 2021; 22(12): e6351.

Copyright

(Copyright © 2021, Molecular Diversity Preservation International)

DOI

10.3390/ijms22126351

PMID

34198546

PMCID

PMC8231800

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. In COPD, the relationship between the neutrophil serine protease, neutrophil elastase, and its endogenous inhibitor, alpha-1-antitrypsin (AAT) is the best characterised. AAT belongs to a superfamily of serine protease inhibitors known as serpins. Advances in screening technologies have, however, resulted in many members of the serpin superfamily being identified as having differential expression across a multitude of chronic lung diseases compared to healthy individuals. Serpins exhibit a unique suicide-substrate mechanism of inhibition during which they undergo a dramatic conformational change to a more stable form. A limitation is that this also renders them susceptible to disease-causing mutations. Identification of the extent of their physiological/pathological role in the airways would allow further expansion of knowledge regarding the complexity of protease regulation in the lung and may provide wider opportunity for their use as therapeutics to aid the management of COPD and other chronic airways diseases.

Language: en

Keywords

Humans; Animals; Disease Models, Animal; serine protease; antiprotease; chronic obstructive pulmonary disease (COPD); protease inhibitor; Pulmonary Disease, Chronic Obstructive; Serine Proteases; serpin; Serpins