The molecular and cellular pathology of α1-antitrypsin deficiency

Gooptu, Bibek and Dickens, J.A. and Lomas, D.A. (2014) The molecular and cellular pathology of α1-antitrypsin deficiency. Trends in Molecular Medicine 20 (2), pp. 116-127. ISSN 1471-4914.

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Official URL: http://dx.doi.org/10.1016/j.molmed.2013.10.007

Abstract

Since its discovery 50 years ago, α1-antitrypsin deficiency has represented a case study in molecular medicine, with careful clinical characterisation guiding genetic, biochemical, biophysical, structural, cellular, and in vivo studies. Here we highlight the milestones in understanding the disease mechanisms and show how they have spurred the development of novel therapeutic strategies. α1-Antitrypsin deficiency is an archetypal conformational disease. Its pathogenesis demonstrates the interplay between protein folding and quality control mechanisms, with aberrant conformational changes causing liver and lung disease through combined loss- and toxic gain-of-function effects. Moreover, α1-antitrypsin exemplifies the ability of diverse proteins to self-associate into a range of morphologically distinct polymers, suggesting a mechanism for protein and cell evolution.

Metadata

Item Type:	Article
Keyword(s) / Subject(s):	α1-antitrypsin deficiency, conformational disease, misfolding, protein evolution, emphysema, cirrhosis
School:	Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
Research Centres and Institutes:	Structural Molecular Biology, Institute of (ISMB)
Depositing User:	Administrator
Date Deposited:	14 Jan 2014 13:40
Last Modified:	02 Aug 2023 17:09
URI:	https://eprints.bbk.ac.uk/id/eprint/8958

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