Peer Reviewed

1

Document Type

Article

Publication Date

1-6-2011

Keywords

Animals, Endoplasmic Reticulum, Genetic Predisposition to Disease, Heterozygote, Humans, Lung, Lung Diseases, Mutation, Peptide Hydrolases, Phenotype, Pulmonary Disease, Chronic Obstructive, Risk Assessment, Risk Factors, Smoking, Stress, Physiological, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency

Comments

The Version of Scholarly Record of this Article is published in Expert Review of Respiratory Medicine 2011, available online at: http://www.tandfonline.com/ DOI: 10.1586/ers.11.20

Abstract

The serine proteinase inhibitor α-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.

Disciplines

Medicine and Health Sciences

Citation

Greene CM, Hassan T, Molloy K, McElvaney NG. The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency. Expert Review of Respiratory Medicine. 2011;5(3):395-411

PubMed ID

21702661

DOI Link

10.1586/ers.11.20

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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