BIROn - Birkbeck Institutional Research Online

    Mechanisms of emphysema in 1-antitrypsin deficiency: molecular and cellular insights

    Gooptu, Bibek and Ekeowa, U.I. and Lomas, D.A. (2009) Mechanisms of emphysema in 1-antitrypsin deficiency: molecular and cellular insights. European Respiratory Journal 34 (2), pp. 475-488. ISSN 0903-1936.

    Full text not available from this repository.

    Abstract

    The severe, early onset emphysema that occurs in patients with circulating deficiency of α1-antitrypsin (α1-AT) attests to the importance of this protease inhibitor in maintaining lung parenchymal integrity. It has led to the powerful concept of protease:antiprotease balance being crucial to alveolar homeostasis. Pathogenic mutations cause α1-AT to self-associate into polymer chains that accumulate intracellularly rather than proceeding along the secretory pathway. Polymerisation of α1-AT abolishes antiprotease activity and confers toxic gain-of-function effects. Since α1-AT is predominantly synthesised in the liver, where it does not play a major homeostatic role, the directly toxic effects of polymerisation are clearest here. However, data from molecular, cellular, animal and ex vivo studies indicate that intrapulmonary polymerisation of α1-AT and inflammatory positive feedback loops may augment the destructive effects of decreased antiprotease levels in the lung. This review integrates the findings from these different approaches and highlights how multiple pathways may converge to give the severe, panacinar emphysema phenotype seen in α1-AT deficiency.

    Metadata

    Item Type: Article
    Keyword(s) / Subject(s): α1-Antitrypsin, deficiency, elastase, interstitial, inflammation, lung, mechanism of emphysema, serpin, polymer
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 24 Jun 2015 14:56
    Last Modified: 06 Dec 2016 10:42
    URI: http://eprints.bbk.ac.uk/id/eprint/12434

    Statistics

    Downloads
    Activity Overview
    0Downloads
    116Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item