ArticleNature medicine2017
Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 110 papers.
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.
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Who cites it
110 citing papers in PubMed, 216 citations in OpenAlex.
- The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial.Hepatology (Baltimore, Md.) · 2018Trial
- Advances in pharmacological interventions for hepatic fibrosis: from pathogenic mechanisms to novel therapeutic targets.Annals of medicine · 2026Review
- Review
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- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- c-FLIP Protects Cardiac Microcirculation in Sepsis-Induced Myocardial Dysfunction Via FUNDC1-Mediated Regulation of Mitochondrial Autophagy.JACC. Basic to translational science · 2025Article
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- At the Crossroads of Health and Disease: Consequences of Fat in the Liver.Annual review of physiology · 2025Review
- FTO Alleviates Hepatic Ischemia-Reperfusion Injury by Regulating Apoptosis and Autophagy.Gastroenterology research and practice · 2025Article
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models.Animal models and experimental medicine · 2025Article
- Unveiling the hidden risk of caspofungin: insights from three adverse event reporting systems and network pharmacology integration.Frontiers in pharmacology · 2025Article
- ALKBH5 Protects Against Hepatic Ischemia-Reperfusion Injury by Regulating YTHDF1-Mediated YAP Expression.International journal of molecular sciences · 2024Article
- The Regulatory Impact of CFLAR Methylation Modification on Liver Lipid Metabolism.International journal of molecular sciences · 2024Article
- From NAFLD to NASH: Understanding the spectrum of non-alcoholic liver diseases and their consequences.Heliyon · 2024Review
- The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review.Biomolecules · 2024Review
- Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.Frontiers in cell and developmental biology · 2024Review
- Chinese herbal formula in the treatment of metabolic dysfunction-associated steatotic liver disease: current evidence and practice.Frontiers in medicine · 2024Review
- Unveiling the role of ferroptosis in the progression from NAFLD to NASH: recent advances in mechanistic understanding.Frontiers in endocrinology · 2024Review
- Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
22 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic steatohepatitis (NASH) is a progressive disease that is often accompanied by metabolic syndrome and poses a high risk of severe liver damage. However, no effective pharmacological treatment is currently available for NASH. Here we report that CASP8 and FADD-like apoptosis regulator (CFLAR) is a key suppressor of steatohepatitis and its metabolic disorders. We provide mechanistic evidence that CFLAR directly targets the kinase MAP3K5 (also known as ASK1) and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and the kinase MAPK8 (also known as JNK1). Furthermore, we identified a small peptide segment in CFLAR that effectively attenuates the progression of steatohepatitis and metabolic disorders in both mice and monkeys by disrupting the N-terminus-mediated dimerization of ASK1 when the peptide is expressed from an injected adenovirus-associated virus 8-based vector. Taken together, these findings establish CFLAR as a key suppressor of steatohepatitis and indicate that the development of CFLAR-peptide-mimicking drugs and the screening of small-molecular inhibitors that specifically block ASK1 dimerization are new and feasible approaches for NASH treatment.
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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.