Document Type

Article

Publication Date

2-1-2008

Keywords

Animals, Autophagy, Humans, Liver Diseases, Lung Diseases, Models, Biological, Protein Conformation, Protein Folding, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency

Comments

The original publication is available at www.springerlink.com

Abstract

Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 mumol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called 'Z' mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols.

Disciplines

Medicine and Health Sciences

Citation

Greene CM, Miller SDW, Carroll T, McLean C, O'Mahony M, Lawless MW, O'Neill SJ, Taggart CC, McElvaney NG. Alpha-1 antitrypsin deficiency: a conformational disease associated with lung and liver manifestations. Journal of Inherited Metababolic Disorders 2008;31(1):21-34.

PubMed ID

18193338

DOI Link

10.1007/s10545-007-0748-y