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Article ; Online: Therapeutic exploitation of ferroptosis.

Walravens, Magali / Koeken, Ine / Vanden Berghe, Tom

2024 Volume 52, Issue 2, Page(s) 693–706

Abstract: Pathological breakdown of membrane lipids through excessive lipid peroxidation (LPO) was first described in the mid-20th century and is now recognized as a form of regulated cell death, dubbed ferroptosis. Accumulating evidence unveils how metabolic ... ...

Abstract	Pathological breakdown of membrane lipids through excessive lipid peroxidation (LPO) was first described in the mid-20th century and is now recognized as a form of regulated cell death, dubbed ferroptosis. Accumulating evidence unveils how metabolic regulation restrains peroxidation of phospholipids within cellular membranes, thereby impeding ferroptosis execution. Unleashing these metabolic breaks is currently therapeutically explored to sensitize cancers to ferroptosis inducing anti-cancer therapies. Reversely, these natural ferroptotic defense mechanisms can fail resulting in pathological conditions or diseases such as ischemia-reperfusion injury, multi-organ dysfunction, stroke, infarction, or neurodegenerative diseases. This minireview outlines current ferroptosis-inducing anti-cancer strategies and highlights the detection as well as the therapeutic targeting of ferroptosis in preclinical experimental settings. Herein, we also briefly summarize observations related to LPO, iron and redox deregulation in patients that might hint towards ferroptosis as a contributing factor.
MeSH term(s)	Ferroptosis ; Humans ; Lipid Peroxidation ; Neoplasms/metabolism ; Neoplasms/drug therapy ; Animals ; Iron/metabolism ; Oxidation-Reduction ; Antineoplastic Agents/therapeutic use ; Reperfusion Injury/metabolism ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/drug therapy
Chemical Substances	Iron (E1UOL152H7) ; Antineoplastic Agents
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20230550
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Zs.A 944: Show issues

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Article ; Online: Emerging role of ferroptosis in metabolic dysfunction-associated steatotic liver disease: revisiting hepatic lipid peroxidation.

Peleman, Cédric / Francque, Sven / Berghe, Tom Vanden

EBioMedicine

2024 Volume 102, Page(s) 105088

Abstract: Metabolic dysfunction-associated steatohepatitis (MASH) is characterised by cell death of parenchymal liver cells which interact with their microenvironment to drive disease activity and liver fibrosis. The identification of the major death type could ... ...

Abstract	Metabolic dysfunction-associated steatohepatitis (MASH) is characterised by cell death of parenchymal liver cells which interact with their microenvironment to drive disease activity and liver fibrosis. The identification of the major death type could pave the way towards pharmacotherapy for MASH. To date, increasing evidence suggest a type of regulated cell death, named ferroptosis, which occurs through iron-catalysed peroxidation of polyunsaturated fatty acids (PUFA) in membrane phospholipids. Lipid peroxidation enjoys renewed interest in the light of ferroptosis, as druggable target in MASH. This review recapitulates the molecular mechanisms of ferroptosis in liver physiology, evidence for ferroptosis in human MASH and critically appraises the results of ferroptosis targeting in preclinical MASH models. Rewiring of redox, iron and PUFA metabolism in MASH creates a proferroptotic environment involved in MASH-related hepatocellular carcinoma (HCC) development. Ferroptosis induction might be a promising novel approach to eradicate HCC, while its inhibition might ameliorate MASH disease progression.
MeSH term(s)	Humans ; Lipid Peroxidation ; Carcinoma, Hepatocellular/pathology ; Ferroptosis ; Liver Neoplasms/pathology ; Iron/metabolism ; Fatty Liver/etiology ; Tumor Microenvironment
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2024-03-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2024.105088
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Article ; Online: A guide to ferroptosis, the biological rust of cellular membranes.

Veeckmans, Geraldine / Van San, Emily / Vanden Berghe, Tom

The FEBS journal

2023

Abstract: Unprotected iron can rust due to oxygen exposure. Similarly, in our body, oxidative stress can kill cells in an iron-dependent manner, which can give rise to devastating diseases. This type of cell death is referred to as ferroptosis. Generally, ... ...

Abstract	Unprotected iron can rust due to oxygen exposure. Similarly, in our body, oxidative stress can kill cells in an iron-dependent manner, which can give rise to devastating diseases. This type of cell death is referred to as ferroptosis. Generally, ferroptosis is defined as an iron-catalyzed form of regulated necrosis that occurs through excessive peroxidation of polyunsaturated fatty acids within cellular membranes. This review summarizes how ferroptosis is executed by a rather primitive biochemical process, under tight regulation of lipid, iron, and redox metabolic processes. An overview is given of major classes of ferroptosis inducers and inhibitors, and how to detect ferroptosis. Finally, its detrimental role in disease is briefly discussed.
Language	English
Publishing date	2023-11-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16993
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Zs.A 260: Show issues

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Article ; Online: Improving cardiac differentiation of human pluripotent stem cells by targeting ferroptosis.

Aalders, Jeffrey / Léger, Laurens / Hassannia, Behrouz / Goossens, Vera / Vanden Berghe, Tom / van Hengel, Jolanda

Regenerative therapy

2024 Volume 27, Page(s) 21–31

Abstract: Generation of cardiomyocytes from human pluripotent stem cells (hPSCs) is of high interest for disease modelling and regenerative medicine. hPSCs can provide an unlimited source of patient-specific cardiomyocytes that are otherwise difficult to obtain ... ...

Abstract	Generation of cardiomyocytes from human pluripotent stem cells (hPSCs) is of high interest for disease modelling and regenerative medicine. hPSCs can provide an unlimited source of patient-specific cardiomyocytes that are otherwise difficult to obtain from individuals. Moreover, the low proliferation rate of adult cardiomyocytes and low viability
Language	English
Publishing date	2024-03-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2835333-X
ISSN	2352-3204 ; 2352-3204
ISSN (online)	2352-3204
ISSN	2352-3204
DOI	10.1016/j.reth.2024.02.007
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Article ; Online: Beyond ferrostatin-1: a comprehensive review of ferroptosis inhibitors.

Scarpellini, Camilla / Klejborowska, Greta / Lanthier, Caroline / Hassannia, Behrouz / Vanden Berghe, Tom / Augustyns, Koen

Trends in pharmacological sciences

2023 Volume 44, Issue 12, Page(s) 902–916

Abstract: Ferroptosis is an iron-catalysed form of regulated cell death, which is critically dependent on phospholipid peroxidation of cellular membranes. Ferrostatin 1 was one of the first synthetic radical-trapping antioxidants (RTAs) reported to block ... ...

Abstract	Ferroptosis is an iron-catalysed form of regulated cell death, which is critically dependent on phospholipid peroxidation of cellular membranes. Ferrostatin 1 was one of the first synthetic radical-trapping antioxidants (RTAs) reported to block ferroptosis and it is widely used as reference compound. Ferroptosis has been linked to multiple diseases and the use of its inhibitors could have therapeutic potential. Although, novel biochemical pathways provide insights for different pharmacological targets, the use of lipophilic RTAs to block ferroptosis remains superior. In this Review, we provide a comprehensive overview of the different classes of ferroptosis inhibitors, focusing on endogenous and synthetic RTAs. A thorough analysis of their chemical, pharmacokinetic, and pharmacological properties and potential for in vivo use is provided.
MeSH term(s)	Humans ; Ferroptosis ; Lipid Peroxidation ; Cyclohexylamines/metabolism ; Cyclohexylamines/pharmacology ; Antioxidants/pharmacology
Chemical Substances	ferrostatin-1 ; Cyclohexylamines ; Antioxidants
Language	English
Publishing date	2023-09-26
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	282846-7
ISSN	1873-3735 ; 0165-6147
ISSN (online)	1873-3735
ISSN	0165-6147
DOI	10.1016/j.tips.2023.08.012
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Zs.A 1513: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Ferroptosis: Biological Rust of Lipid Membranes.

Hassannia, Behrouz / Van Coillie, Samya / Vanden Berghe, Tom

Antioxidants & redox signaling

2020 Volume 35, Issue 6, Page(s) 487–509

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Animals ; Ferroptosis ; Humans ; Membrane Lipids/metabolism
Chemical Substances	Membrane Lipids
Language	English
Publishing date	2020-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2020.8175
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Zs.A 5488: Show issues

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Book ; Online ; Thesis: Regulated necrosis in the adrenal glands and the kidney

Belavgeni, Alexia [Verfasser] / Wielockx, Ben [Gutachter] / Vanden Berghe, Tom [Gutachter]

2022

Author's details	Alexia Belavgeni ; Gutachter: Ben Wielockx, Tom Vanden Berghe
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Technische Universität Dresden
Publishing place	Dresden
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Loss of PPARα function promotes epigenetic dysregulation of lipid homeostasis driving ferroptosis and pyroptosis lipotoxicity in metabolic dysfunction associated Steatotic liver disease (MASLD)

Claudia Theys / Tineke Vanderhaeghen / Evelien Van Dijck / Cedric Peleman / Anne Scheepers / Joe Ibrahim / Ligia Mateiu / Steven Timmermans / Tom Vanden Berghe / Sven M. Francque / Wim Van Hul / Claude Libert / Wim Vanden Berghe

Frontiers in Molecular Medicine, Vol

2024 Volume 3

Abstract: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a growing epidemic with an estimated prevalence of 20%–30% in Europe and the most common cause of chronic liver disease worldwide. The onset and progression of MASLD are orchestrated by ... ...

Abstract	Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a growing epidemic with an estimated prevalence of 20%–30% in Europe and the most common cause of chronic liver disease worldwide. The onset and progression of MASLD are orchestrated by an interplay of the metabolic environment with genetic and epigenetic factors. Emerging evidence suggests altered DNA methylation pattern as a major determinant of MASLD pathogenesis coinciding with progressive DNA hypermethylation and gene silencing of the liver-specific nuclear receptor PPARα, a key regulator of lipid metabolism. To investigate how PPARα loss of function contributes to epigenetic dysregulation in MASLD pathology, we studied DNA methylation changes in liver biopsies of WT and hepatocyte-specific PPARα KO mice, following a 6-week CDAHFD (choline-deficient, L-amino acid-defined, high-fat diet) or chow diet. Interestingly, genetic loss of PPARα function in hepatocyte-specific KO mice could be phenocopied by a 6-week CDAHFD diet in WT mice which promotes epigenetic silencing of PPARα function via DNA hypermethylation, similar to MASLD pathology. Remarkably, genetic and lipid diet-induced loss of PPARα function triggers compensatory activation of multiple lipid sensing transcription factors and epigenetic writer-eraser-reader proteins, which promotes the epigenetic transition from lipid metabolic stress towards ferroptosis and pyroptosis lipid hepatoxicity pathways associated with advanced MASLD. In conclusion, we show that PPARα function is essential to support lipid homeostasis and to suppress the epigenetic progression of ferroptosis-pyroptosis lipid damage associated pathways towards MASLD fibrosis.
Keywords	PPARα ; MASLD ; epigenetics ; lipid metabolism ; bile acid metabolism ; NAFLD ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	570
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Paving the way for precision medicine v2.0 in intensive care by profiling necroinflammation in biofluids.

Vanden Berghe, Tom / Hoste, Eric

Cell death and differentiation

2018 Volume 26, Issue 1, Page(s) 83–98

Abstract: Current clinical diagnosis is typically based on a combination of approaches including clinical examination of the patient, clinical experience, physiologic and/or genetic parameters, high-tech diagnostic medical imaging, and an extended list of ... ...

Abstract	Current clinical diagnosis is typically based on a combination of approaches including clinical examination of the patient, clinical experience, physiologic and/or genetic parameters, high-tech diagnostic medical imaging, and an extended list of laboratory values mostly determined in biofluids such as blood and urine. One could consider this as precision medicine v1.0. However, recent advances in technology and better understanding of molecular mechanisms underlying disease will allow us to better characterize patients in the future. These improvements will enable us to distinguish patients who have similar clinical presentations but different cellular and molecular responses. Treatments will be able to be chosen more "precisely", resulting in more appropriate therapy, precision medicine v2.0. In this review, we will reflect on the potential added value of recent advances in technology and a better molecular understanding of necrosis and inflammation for improving diagnosis and treatment of critically ill patients. We give a brief overview on the mutual interplay between necrosis and inflammation, which are two crucial detrimental factors in organ and/or systemic dysfunction. One of the challenges for the future will thus be the cellular and molecular profiling of necroinflammation in biofluids. The huge amount of data generated by profiling biomolecules and single cells through, for example, different omic-approaches is needed for data mining methods to allow patient-clustering and identify novel biomarkers. The real-time monitoring of biomarkers will allow continuous (re)evaluation of treatment strategies using machine learning models. Ultimately, we may be able to offer precision therapies specifically designed to target the molecular set-up of an individual patient, as has begun to be done in cancer therapeutics.
MeSH term(s)	Animals ; Big Data ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/cerebrospinal fluid ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/urine ; Critical Care ; Humans ; Inflammation/immunology ; Inflammation/physiopathology ; Machine Learning ; Mice ; Multiple Organ Failure/immunology ; Multiple Organ Failure/physiopathology ; Multiple Organ Failure/therapy ; Necrosis/immunology ; Necrosis/physiopathology ; Precision Medicine
Chemical Substances	Biomarkers, Tumor
Keywords	covid19
Language	English
Publishing date	2018-09-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/s41418-018-0196-2
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Zs.A 4230: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug.

Hassannia, Behrouz / Logie, Emilie / Vandenabeele, Peter / Vanden Berghe, Tom / Vanden Berghe, Wim

Biochemical pharmacology

2019 Volume 173, Page(s) 113602

Abstract: Despite the recent successes of targeted cancer immuno-therapies, drug resistance and disease relapse remain a huge burden in cancer patient treatment. This has fueled renewed interest in natural product discovery to identify new pharmacophores for ... ...

Abstract	Despite the recent successes of targeted cancer immuno-therapies, drug resistance and disease relapse remain a huge burden in cancer patient treatment. This has fueled renewed interest in natural product discovery to identify new pharmacophores for innovative cancer drug development. Reverse pharmacology approaches of Withania somnifera leaves and roots (alternatively also called Ashwagandha or Indian ginseng in traditional Ayurvedic and Unani folk medicine) have identified Withaferin A (WA) as the most bioactive compound for treatment of inflammatory ailments, supporting traditional use of their corresponding extracts in indigenous medicine. In this review we summarize preclinical in vivo evidence for therapeutic cancer applications of WA and provide a biochemical framework of its polypharmaceutical effects against cancer hallmarks.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Humans ; Medicine, Ayurvedic/methods ; Molecular Structure ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Phytotherapy/methods ; Withania/chemistry ; Withanolides/chemistry ; Withanolides/pharmacokinetics ; Withanolides/pharmacology ; Xenograft Model Antitumor Assays/methods
Chemical Substances	Withanolides ; withaferin A (L6DO3QW4K5)
Language	English
Publishing date	2019-08-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2019.08.004
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