Journal article
The anticonvulsive Phenhydan (R) suppresses extrinsic cell death
Caroline Moerke, Isabel Jaco, Christin Dewitz, Tammo Mueller, Annette Jacobsen, Jeremie Gautheron, Juergen Fritsch, Jessica Schmitz, Jan Hinrich Braesen, Claudia Guenther, James M Murphy, Ulrich Kunzendorf, Pascal Meier, Stefan Krautwald
Cell Death & Differentiation | NATURE PUBLISHING GROUP | Published : 2019
Abstract
Different forms of regulated cell death-like apoptosis and necroptosis contribute to the pathophysiology of clinical conditions including ischemia-reperfusion injury, myocardial infarction, sepsis, and multiple sclerosis. In particular, the kinase activity of the receptor-interacting serine/threonine protein kinase 1 (RIPK1) is crucial for cell fate in inflammation and cell death. However, despite its involvement in pathological conditions, no pharmacologic inhibitor of RIPK1-mediated cell death is currently in clinical use. Herein, we screened a collection of clinical compounds to assess their ability to modulate RIPK1-mediated cell death. Our small-scale screen identified the anti-epilepsy..
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Grants
Awarded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Awarded by Fondation pour la recherche Medicale
Awarded by Institute of Cardiometabolism and Nutrition
Awarded by National Health and Medical Research Council of Australia
Awarded by World Wide Cancer Research grant
Awarded by Breast Cancer Now
Awarded by ERC
Funding Acknowledgements
We thank Maike Berger, Janina Kahl, Katja Bruch, and Parvin Davarnia for excellent technical assistance. We also thank the former lab member Federica De Zen, who contributed to the concept at the initial phase of the study. SK is supported by a grant provided by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Projektnummer: 400339789 [KR 1690/6-1]). This work was additionally funded by the Medical Faculty of CAU Kiel, Germany (to CM and SK), and Dr. Werner Jackstadt-Stiftung (to SK). AVJ is supported by an Australian Government Research Training Program Scholarship. JG is supported by the Fondation pour la recherche Medicale (FRM-ARF20170938613) and the Institute of Cardiometabolism and Nutrition (ICAN-PAP17NCEJG). JMM acknowledges funding from the National Health and Medical Research Council of Australia (1124735, 1105754, and IRIISS 9000433) and Victorian Government Operational Infrastructure Support. The Meier lab is supported by a World Wide Cancer Research grant (14-1328) and Breast Cancer Now CTR-QR14-007. PM acknowledges NHS funding to the NIHR Biomedical Research Centre and from the ERC (grant agreement no. 323040).