| Autor: |
Kelly-Robinson GA; School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT9 7BL, UK., Reihill JA; School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT9 7BL, UK., Lundy FT; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland BT9 7BL, UK., McGarvey LP; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland BT9 7BL, UK., Lockhart JC; Institute for Biomedical and Environmental Health Research, School of Health and Life Sciences, University of the West of Scotland, Paisley, Scotland PA1 2BE, UK., Litherland GJ; Institute for Biomedical and Environmental Health Research, School of Health and Life Sciences, University of the West of Scotland, Paisley, Scotland PA1 2BE, UK., Thornbury KD; Smooth Muscle Research Centre, Dundalk Institute of Technology, A91 HRK2 Dundalk, Ireland., Martin SL; School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT9 7BL, UK. |
| Abstrakt: |
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. |
