The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases
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 endo...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/12/6351 |
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| author | Gillian A. Kelly-Robinson James A. Reihill Fionnuala T. Lundy Lorcan P. McGarvey John C. Lockhart Gary J. Litherland Keith D. Thornbury S. Lorraine Martin |
| author_facet | Gillian A. Kelly-Robinson James A. Reihill Fionnuala T. Lundy Lorcan P. McGarvey John C. Lockhart Gary J. Litherland Keith D. Thornbury S. Lorraine Martin |
| author_sort | Gillian A. Kelly-Robinson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:25:09Z |
| format | Article |
| id | doaj.art-21c93c68852c4eeca0215a3ab6951ea2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:25:09Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-21c93c68852c4eeca0215a3ab6951ea22023-11-22T00:01:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212635110.3390/ijms22126351The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung DiseasesGillian A. Kelly-Robinson0James A. Reihill1Fionnuala T. Lundy2Lorcan P. McGarvey3John C. Lockhart4Gary J. Litherland5Keith D. Thornbury6S. Lorraine Martin7School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland BT9 7BL, UKWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland BT9 7BL, UKWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland BT9 7BL, UKInstitute for Biomedical and Environmental Health Research, School of Health and Life Sciences, University of the West of Scotland, Paisley, Scotland PA1 2BE, UKInstitute for Biomedical and Environmental Health Research, School of Health and Life Sciences, University of the West of Scotland, Paisley, Scotland PA1 2BE, UKSmooth Muscle Research Centre, Dundalk Institute of Technology, A91 HRK2 Dundalk, IrelandSchool of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland BT9 7BL, UKChronic 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.https://www.mdpi.com/1422-0067/22/12/6351serine proteaseserpinprotease inhibitorchronic obstructive pulmonary disease (COPD)antiprotease |
| spellingShingle | Gillian A. Kelly-Robinson James A. Reihill Fionnuala T. Lundy Lorcan P. McGarvey John C. Lockhart Gary J. Litherland Keith D. Thornbury S. Lorraine Martin The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases International Journal of Molecular Sciences serine protease serpin protease inhibitor chronic obstructive pulmonary disease (COPD) antiprotease |
| title | The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases |
| title_full | The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases |
| title_fullStr | The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases |
| title_full_unstemmed | The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases |
| title_short | The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases |
| title_sort | serpin superfamily and their role in the regulation and dysfunction of serine protease activity in copd and other chronic lung diseases |
| topic | serine protease serpin protease inhibitor chronic obstructive pulmonary disease (COPD) antiprotease |
| url | https://www.mdpi.com/1422-0067/22/12/6351 |
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