The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency

Catherine M. Greene, Hassan Tidi Maharani, Kevin Molloy, Noel G. McElvaney

Research output: Contribution to journalReview article

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)395-411
Number of pages17
JournalExpert Review of Respiratory Medicine
Volume5
Issue number3
DOIs
Publication statusPublished - Jun 2011
Externally publishedYes

Fingerprint

Endoplasmic Reticulum Stress
Protease Inhibitors
Trypsin
Chronic Obstructive Pulmonary Disease
Lung Diseases
Peptide Hydrolases
Mutation
Serine Proteinase Inhibitors
Endoplasmic Reticulum
Hepatocytes
Smoking
Genes

Keywords

  • α-1 anti-trypsin deficiency
  • augmentation therapy
  • endoplasmic reticulum stress
  • serine antiprotease
  • serine proteases
  • SERPINA1 heterozygosity

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Immunology and Allergy
  • Public Health, Environmental and Occupational Health

Cite this

The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency. / Greene, Catherine M.; Tidi Maharani, Hassan; Molloy, Kevin; McElvaney, Noel G.

In: Expert Review of Respiratory Medicine, Vol. 5, No. 3, 06.2011, p. 395-411.

Research output: Contribution to journalReview article

Greene, Catherine M. ; Tidi Maharani, Hassan ; Molloy, Kevin ; McElvaney, Noel G. / The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency. In: Expert Review of Respiratory Medicine. 2011 ; Vol. 5, No. 3. pp. 395-411.
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