Greene, Catherine M. Hassan, Tidi Molloy, Kevin McElvaney, Noel G. The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency. <p>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.</p> 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;Medicine 2019-11-22
    https://repository.rcsi.com/articles/journal_contribution/The_role_of_proteases_endoplasmic_reticulum_stress_and_SERPINA1_heterozygosity_in_lung_disease_and_-1_anti-trypsin_deficiency_/10785686