ArticleEMBO molecular medicine2013
Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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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
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.Nature communications · 2020Pooled it
- Polymeric alpha-1 antitrypsin perturbs Paneth cell proteostasis and exacerbates intestinal inflammation.Signal transduction and targeted therapy · 2026Article
- p62/SQSTM1-KEAP1 complex prevents clearance of ubiquitinated Z alpha-1 antitrypsin and aggravates liver proteotoxicity.The Journal of biological chemistry · 2026Article
- Stereo-random oligonucleotides enable efficient recruitment of ADAR in vitro and in vivo.Nature communications · 2025Article
- Autophagy in cancer and protein conformational disorders.FEBS letters · 2025Review
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- USF2 and TFEB compete in regulating lysosomal and autophagy genes.Nature communications · 2024Article
- Sestrin2 drives ER-phagy in response to protein misfolding.Developmental cell · 2024Article
- ER-to-lysosome-associated degradation acts as failsafe mechanism upon ERAD dysfunction.EMBO reports · 2024Article
- Mitophagy in human health, ageing and disease.Nature metabolism · 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
- Article
- Protein quality control and aggregation in the endoplasmic reticulum: From basic to bedside.Frontiers in cell and developmental biology · 2023Review
- TFEB regulates sulfur amino acid and coenzyme A metabolism to support hepatic metabolic adaptation and redox homeostasis.Nature communications · 2022Article
- Global 5'-UTR RNA structure regulates translation of a SERPINA1 mRNA.Nucleic acids research · 2022Article
- Role of TFEB in Autophagy and the Pathogenesis of Liver Diseases.Biomolecules · 2022Review
- Review
- Autophagy in major human diseases.The EMBO journal · 2021Review
- N-glycan processing selects ERAD-resistant misfolded proteins for ER-to-lysosome-associated degradation.The EMBO journal · 2021Article
- Genistein Activates Transcription Factor EB and Corrects Niemann-Pick C Phenotype.International journal of molecular sciences · 2021Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Alpha-1-anti-trypsin deficiency is the most common genetic cause of liver disease in children and liver transplantation is currently the only available treatment. Enhancement of liver autophagy increases degradation of mutant, hepatotoxic alpha-1-anti-trypsin (ATZ). We investigated the therapeutic potential of liver-directed gene transfer of transcription factor EB (TFEB), a master gene that regulates lysosomal function and autophagy, in PiZ transgenic mice, recapitulating the human hepatic disease. Hepatocyte TFEB gene transfer resulted in dramatic reduction of hepatic ATZ, liver apoptosis and fibrosis, which are key features of alpha-1-anti-trypsin deficiency. Correction of the liver phenotype resulted from increased ATZ polymer degradation mediated by enhancement of autophagy flux and reduced ATZ monomer by decreased hepatic NFκB activation and IL-6 that drives ATZ gene expression. In conclusion, TFEB gene transfer is a novel strategy for treatment of liver disease of alpha-1-anti-trypsin deficiency. This study may pave the way towards applications of TFEB gene transfer for treatment of a wide spectrum of human disorders due to intracellular accumulation of toxic proteins.
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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.