Protein misfolding and obstructive lung disease.

Hdl Handle:
http://hdl.handle.net/10147/126118
Title:
Protein misfolding and obstructive lung disease.
Authors:
Greene, Catherine M; McElvaney, Noel G
Affiliation:
Respiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ie
Citation:
Protein misfolding and obstructive lung disease. 2010, 7 (6):346-55 Proc Am Thorac Soc
Journal:
Proceedings of the American Thoracic Society
Issue Date:
Nov-2010
URI:
http://hdl.handle.net/10147/126118
DOI:
10.1513/pats.201002-019AW
PubMed ID:
21030512
Abstract:
The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.
Item Type:
Article
Language:
en
MeSH:
Humans; Lung Diseases, Obstructive; Protein Folding; Proteostasis Deficiencies
ISSN:
1943-5665

Full metadata record

DC FieldValue Language
dc.contributor.authorGreene, Catherine Men
dc.contributor.authorMcElvaney, Noel Gen
dc.date.accessioned2011-03-29T14:50:55Z-
dc.date.available2011-03-29T14:50:55Z-
dc.date.issued2010-11-
dc.identifier.citationProtein misfolding and obstructive lung disease. 2010, 7 (6):346-55 Proc Am Thorac Socen
dc.identifier.issn1943-5665-
dc.identifier.pmid21030512-
dc.identifier.doi10.1513/pats.201002-019AW-
dc.identifier.urihttp://hdl.handle.net/10147/126118-
dc.description.abstractThe endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.-
dc.language.isoenen
dc.subject.meshHumans-
dc.subject.meshLung Diseases, Obstructive-
dc.subject.meshProtein Folding-
dc.subject.meshProteostasis Deficiencies-
dc.titleProtein misfolding and obstructive lung disease.en
dc.typeArticleen
dc.contributor.departmentRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ieen
dc.identifier.journalProceedings of the American Thoracic Societyen
dc.description.provinceLeinster-

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