دورية أكاديمية
Cysteamine-bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis.
| العنوان: | Cysteamine-bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis. |
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| المؤلفون: | Jamalpoor A; Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., van Gelder CA; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Netherlands Proteomics Center, Utrecht, The Netherlands., Yousef Yengej FA; Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands., Zaal EA; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Division of Cell Biology, Cancer & Metabolism, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Berlingerio SP; Department of Pediatric Nephrology & Growth and Regeneration, University Hospitals Leuven & KU Leuven, Leuven, Belgium., Veys KR; Department of Pediatric Nephrology & Growth and Regeneration, University Hospitals Leuven & KU Leuven, Leuven, Belgium., Pou Casellas C; Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Voskuil K; Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Essa K; Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Ammerlaan CM; Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands., Rega LR; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., van der Welle RE; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Lilien MR; Department of Pediatric Nephrology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands., Rookmaaker MB; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands., Clevers H; Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands., Klumperman J; Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Levtchenko E; Department of Pediatric Nephrology & Growth and Regeneration, University Hospitals Leuven & KU Leuven, Leuven, Belgium., Berkers CR; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Division of Cell Biology, Cancer & Metabolism, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Verhaar MC; Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands., Altelaar M; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Netherlands Proteomics Center, Utrecht, The Netherlands., Masereeuw R; Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Janssen MJ; Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands. |
| المصدر: | EMBO molecular medicine [EMBO Mol Med] 2021 Jul 07; Vol. 13 (7), pp. e13067. Date of Electronic Publication: 2021 Jun 24. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: EMBO Press Country of Publication: England NLM ID: 101487380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2024- : Heidelberg : EMBO Press Original Publication: Chichester, West Sussex : Wiley-Blackwell |
| مواضيع طبية MeSH: | Amino Acid Transport Systems, Neutral*/genetics , Cystinosis*/drug therapy, Anilides ; Animals ; Cysteamine ; Humans ; Nitriles ; Phenotype ; Tosyl Compounds ; Zebrafish |
| مستخلص: | Nephropathic cystinosis is a severe monogenic kidney disorder caused by mutations in CTNS, encoding the lysosomal transporter cystinosin, resulting in lysosomal cystine accumulation. The sole treatment, cysteamine, slows down the disease progression, but does not correct the established renal proximal tubulopathy. Here, we developed a new therapeutic strategy by applying omics to expand our knowledge on the complexity of the disease and prioritize drug targets in cystinosis. We identified alpha-ketoglutarate as a potential metabolite to bridge cystinosin loss to autophagy, apoptosis and kidney proximal tubule impairment in cystinosis. This insight combined with a drug screen revealed a bicalutamide-cysteamine combination treatment as a novel dual-target pharmacological approach for the phenotypical correction of cystinotic kidney proximal tubule cells, patient-derived kidney tubuloids and cystinotic zebrafish. (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.) |
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| فهرسة مساهمة: | Keywords: Bicalutamide combination therapy; alpha-ketoglutarate; cysteamine; cystinosis; renal Fanconi syndrome |
| المشرفين على المادة: | 0 (Amino Acid Transport Systems, Neutral) 0 (Anilides) 0 (Nitriles) 0 (Tosyl Compounds) 5UX2SD1KE2 (Cysteamine) A0Z3NAU9DP (bicalutamide) |
| تواريخ الأحداث: | Date Created: 20210624 Date Completed: 20211025 Latest Revision: 20231107 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8261496 |
| DOI: | 10.15252/emmm.202013067 |
| PMID: | 34165243 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1757-4684 |
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| DOI: | 10.15252/emmm.202013067 |