ArticleExperimental biology and medicine (Maywood, N.J.)2010
Rapamycin reduces intrahepatic alpha-1-antitrypsin mutant Z protein polymers and liver injury in a mouse model.
Article in Experimental biology and medicine (Maywood, N.J.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
46 citing papers in PubMed, 119 citations in OpenAlex.
- Liver fibrosis: Pathogenesis and innovative nanoparticle-based therapeutic strategies.International journal of pharmaceutics: X · 2026Review
- Adaptive Regulation of mTOR Activity by AMPK, Akt, and ATF6 Pathways in Pi*Z Alpha-1 Antitrypsin Deficient Hepatocytes.Biomolecules · 2026Article
- RNA editing for the treatment of alpha-1 antitrypsin deficiency.Nucleic acids research · 2026Article
- The p24-family and COPII subunit SEC24C facilitate the clearance of alpha1-antitrypsin Z from the endoplasmic reticulum to lysosomes.Molecular biology of the cell · 2024Article
- Future Perspectives in the Diagnosis and Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency.GE Portuguese journal of gastroenterology · 2023Review
- Increased expression or activation of TRPML1 reduces hepatic storage of toxic Z alpha-1 antitrypsin.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Expression of the Z Variant of α1-Antitrypsin Suppresses Hepatic Cholesterol Biosynthesis in Transgenic Zebrafish.International journal of molecular sciences · 2023Article
- Protein quality control and aggregation in the endoplasmic reticulum: From basic to bedside.Frontiers in cell and developmental biology · 2023Review
- Alpha-1-Antitrypsin Deficiency.Clinical liver disease · 2022Review
- Review
- Protein Misfolding and Aggregation: The Relatedness between Parkinson's Disease and Hepatic Endoplasmic Reticulum Storage Disorders.International journal of molecular sciences · 2021Review
- The Autophagy Pathway: A Critical Route in the Disposal of Alpha 1-Antitrypsin Aggregates That Holds Many Mysteries.International journal of molecular sciences · 2021Review
- Autophagy in liver diseases.World journal of hepatology · 2021Review
- Liver disease with unknown etiology - have you ruled out alpha-1 antitrypsin deficiency?Therapeutic advances in chronic disease · 2021Review
- ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets.Frontiers in molecular biosciences · 2021Review
- Quantitative measurement of the histological features of alpha-1 antitrypsin deficiency-associated liver disease in biopsy specimens.PloS one · 2021Article
- Leveraging Population Genomics for Individualized Correction of the Hallmarks of Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Post-Transcriptional Regulation of Alpha One Antitrypsin by a Proteasome Inhibitor.International journal of molecular sciences · 2020Article
- Update on Alpha-1 Antitrypsin Deficiency in Liver Disease.Clinical liver disease · 2020Review
- Mitophagy in the Pathogenesis of Liver Diseases.Cells · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Alpha-1-antitrypsin (a1AT) deficiency is caused by homozygosity for the a1AT mutant Z gene and occurs in one in 2000 Americans. The Z mutation confers an abnormal conformation on the a1AT mutant Z protein, resulting in accumulation within the endoplasmic reticulum of hepatocytes and chronic liver injury. Autophagy is one of several proteolytic mechanisms activated to cope with this hepatocellular protein burden, and is likely important in disposal of the unique polymerized conformation of the a1AT mutant Z protein, which is thought to be especially injurious to the cell. Recent data indicate that rapamycin may more efficiently upregulate autophagy when given in weekly dose pulses, as compared with a daily regimen. Therefore, we evaluated the effect of rapamycin on PiZ mice, a well-characterized model which recapitulates human a1AT liver disease. Daily dosing had no effect on autophagy, on accumulation of a1AT mutant Z protein or on liver injury. Weekly dosing of rapamycin did increase autophagic activity, as shown by increased numbers of autophagic vacuoles. This was associated with reduction in the intrahepatic accumulation of a1AT mutant Z protein in the polymerized conformation. Markers of hepatocellular injury, including cleavage of caspase 12 and hepatic fibrosis, were also decreased. In conclusion, this is the first report of a successful in vivo method for reduction of intrahepatic a1AT mutant Z polymerized protein. Application of this finding may be therapeutic in patients with a1AT deficiency by reducing the intracellular burden of the polymerized, mutant Z protein and by reducing the progression of liver injury.
Indexed as
Identifiers
What OpenQuestion holds
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.