ReviewProceedings of the American Thoracic Society2010
Proteostasis strategies for restoring alpha1-antitrypsin deficiency.
Review in Proceedings of the American Thoracic Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Pioglitazone reduces hepatic α-1 antitrypsin accumulation through autophagy and AMPK activation in α-1 antitrypsin-deficient mice.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Secretion of functional α1-antitrypsin is cell type dependent: Implications for intramuscular delivery for gene therapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Hepatocyte proteomes reveal the role of protein disulfide isomerase 4 in alpha 1-antitrypsin deficiency.JHEP reports : innovation in hepatology · 2021Article
- Human biomimetic liver microphysiology systems in drug development and precision medicine.Nature reviews. Gastroenterology & hepatology · 2021Review
- Alpha-1 Antitrypsin Deficiency-Mediated Liver Toxicity: Why Do Some Patients Do Poorly? What Do We Know So Far?Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways.International journal of molecular sciences · 2020Review
- How to Avoid a No-Deal ER Exit.Cells · 2019Review
- Measuring the Effect of Histone Deacetylase Inhibitors (HDACi) on the Secretion and Activity of Alpha-1 Antitrypsin.Methods in molecular biology (Clifton, N.J.) · 2017Article
- ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency.PloS one · 2017Article
- Blue journal conference. Aging and susceptibility to lung disease.American journal of respiratory and critical care medicine · 2015Review
- Glycoprotein folding and quality-control mechanisms in protein-folding diseases.Disease models & mechanisms · 2014Review
- Malfolded protein structure and proteostasis in lung diseases.American journal of respiratory and critical care medicine · 2014Article
- Golgi localization of ERManI defines spatial separation of the mammalian glycoprotein quality control system.Molecular biology of the cell · 2011Article
- Protein folding: Protection from the outside.Nature · 2011Article
- Viral serpin therapeutics from concept to clinic.Methods in enzymology · 2011Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
Abstract
The function of the human proteome is defined by the proteostasis network (PN) (Science 2008;319:916; Science 2010;329:766), a biological system that generates, protects, and, where necessary, degrades a protein to optimize the cell, tissue, and organismal response to diet, stress, and aging. Numerous human diseases result from the failure of proteins to fold properly in response to mutation, disrupting the proteome. In the case of the exocytic pathway, this includes proteostasis components that direct folding, and export of proteins from the endoplasmic reticulum (ER). Included here are serpin deficiencies, a class of related diseases that result in a significant reduction of secretion of serine proteinase inhibitors from the liver into serum. In response to misfolding, variants of the serine protease α(1)-antitrypsin (α1AT) fail to exit the ER and are targeted for either ER-associated degradation or autophagic pathways. The challenge for developing α1AT deficiency therapeutics is to understand the PN pathways involved in folding and export. Herein, we review the role of the PN in managing the protein fold and function during synthesis in the ER and trafficking to the cell surface or extracellular space. We highlight the role of the proteostasis boundary to define the operation of the proteome (Annu Rev Biochem 2009;78:959). We discuss how manipulation of folding energetics or the PN by pharmacological intervention could provide multiple routes for restoration of variant α1AT function to the benefit of human health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.