The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.
AffiliationRespiratory Research Division, Department of Medicine, Royal College of Surgeons , in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. , firstname.lastname@example.org
Genetic Predisposition to Disease
Pulmonary Disease, Chronic Obstructive/enzymology/genetics
alpha 1-Antitrypsin Deficiency/*enzymology/genetics/physiopathology
MetadataShow full item record
CitationExpert Rev Respir Med. 2011 Jun;5(3):395-411.
JournalExpert review of respiratory medicine
AbstractThe serine proteinase inhibitor alpha-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.
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