ReviewCold Spring Harbor perspectives in biology2011
Hepatic fibrosis and carcinogenesis in α1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders.
Review in Cold Spring Harbor perspectives in biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Meta-Analysis: Redefining Liver Disease Risk in Heterozygous Alpha-1 Antitrypsin Deficiency.Alimentary pharmacology & therapeutics · 2026Pooled it
- Liver Disease and Prevalence of Liver Transplantation in Adults With ZZ Alpha-1 Antitrypsin Deficiency-A Meta-Analysis.Liver international communications · 2025Article
- Longitudinal Outcomes in Young Patients with Alpha-1-Antitrypsin Deficiency with Native Liver Reveal that Neonatal Cholestasis is a Poor Predictor of Future Portal Hypertension.The Journal of pediatrics · 2020Observational
- Interference of miR-107 with Atg12 is inhibited by HULC to promote metastasis of hepatocellular carcinoma.MedComm · 2020Article
- Correcting the F508del-CFTR variant by modulating eukaryotic translation initiation factor 3-mediated translation initiation.The Journal of biological chemistry · 2018Article
- Intrapleural Gene Therapy for Alpha-1 Antitrypsin Deficiency-Related Lung Disease.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- NorUDCA promotes degradation of α1-antitrypsin mutant Z protein by inducing autophagy through AMPK/ULK1 pathway.PloS one · 2018Article
- Recent advances in understanding liver fibrosis: bridging basic science and individualized treatment concepts.F1000Research · 2018Review
- Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease.Annals of the American Thoracic Society · 2016Review
- Liver tumors in children with metabolic disorders.Translational pediatrics · 2015Review
- Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation.Cell death & disease · 2015Article
- Induced pluripotent stem cells model personalized variations in liver disease resulting from α1-antitrypsin deficiency.Hepatology (Baltimore, Md.) · 2015Article
- Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension.Journal of pediatric gastroenterology and nutrition · 2015Observational
- Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.PloS one · 2015Article
- A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency.Human molecular genetics · 2014Article
- A C. elegans model of human α1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover.Human molecular genetics · 2014Article
- Liver autophagy: much more than just taking out the trash.Nature reviews. Gastroenterology & hepatology · 2014Review
- Appropriateness of newborn screening for α1-antitrypsin deficiency.Journal of pediatric gastroenterology and nutrition · 2014Article
- Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver disease in mice.The Journal of clinical investigation · 2014Article
- Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency.PloS one · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In α1-antitrypsin (AT) deficiency, a point mutation renders a hepatic secretory glycoprotein prone to misfolding and polymerization. The mutant protein accumulates in the endoplasmic reticulum of liver cells and causes hepatic fibrosis and hepatocellular carcinoma by a gain-of-function mechanism. Genetic and/or environmental modifiers determine whether an affected homozygote is susceptible to hepatic fibrosis/carcinoma. Two types of proteostasis mechanisms for such modifiers have been postulated: variation in the function of intracellular degradative mechanisms and/or variation in the signal transduction pathways that are activated to protect the cell from protein mislocalization and/or aggregation. In recent studies we found that carbamazepine, a drug that has been used safely as an anticonvulsant and mood stabilizer, reduces the hepatic load of mutant AT and hepatic fibrosis in a mouse model by enhancing autophagic disposal of this mutant protein. These results provide evidence that pharmacological manipulation of endogenous proteostasis mechanisms is an appealing strategy for chemoprophylaxis in disorders involving gain-of-function mechanisms.
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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.