ReviewMolecular and cellular pediatrics2016
Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.
Review in Molecular and cellular pediatrics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 2022Review
- CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells.Frontiers in physiology · 2021Article
- Cystic Fibrosis Lung Disease in the Aging Population.Frontiers in pharmacology · 2021Review
- Immunomodulatory Effects of Azithromycin Revisited: Potential Applications to COVID-19.Frontiers in immunology · 2021Review
- Drug efficacy and toxicity prediction: an innovative application of transcriptomic data.Cell biology and toxicology · 2020Article
- Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.Redox biology · 2020Review
- Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism.Cells · 2020Article
- Disorders of FZ-CRD; insights towards FZ-CRD folding and therapeutic landscape.Molecular medicine (Cambridge, Mass.) · 2019Review
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Defective proteostasis in celiac disease as a new therapeutic target.Cell death & disease · 2019Review
- Oxidative stress, autophagy and airway ion transport.American journal of physiology. Cell physiology · 2019Review
- Adapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2019Review
- Silencing of the Hsp70-specific nucleotide-exchange factor BAG3 corrects the F508del-CFTR variant by restoring autophagy.The Journal of biological chemistry · 2018Article
- TG2 regulates the heat-shock response by the post-translational modification of HSF1.EMBO reports · 2018Article
- CFTR Deletion Confers Mitochondrial Dysfunction and Disrupts Lipid Homeostasis in Intestinal Epithelial Cells.Nutrients · 2018Article
- Role of second-hand smoke (SHS)-induced proteostasis/autophagy impairment in pediatric lung diseases.Molecular and cellular pediatrics · 2017Article
- Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation.Cell death & disease · 2017Article
- DPAGT1-CDG: Functional analysis of disease-causing pathogenic mutations and role of endoplasmic reticulum stress.PloS one · 2017Article
- Cystic fibrosis lung environment and Pseudomonas aeruginosa infection.BMC pulmonary medicine · 2016Review
- SYVN1, NEDD8, and FBXO2 Proteins Regulate ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitin-mediated Proteasomal Degradation.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.
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