dc.contributor.author | Moerke, C | |
dc.contributor.author | Jaco, I | |
dc.contributor.author | Dewitz, C | |
dc.contributor.author | Müller, T | |
dc.contributor.author | Jacobsen, AV | |
dc.contributor.author | Gautheron, J | |
dc.contributor.author | Fritsch, J | |
dc.contributor.author | Schmitz, J | |
dc.contributor.author | Bräsen, JH | |
dc.contributor.author | Günther, C | |
dc.contributor.author | Murphy, JM | |
dc.contributor.author | Kunzendorf, U | |
dc.contributor.author | Meier, P | |
dc.contributor.author | Krautwald, S | |
dc.date.accessioned | 2019-02-20T07:49:32Z | |
dc.date.issued | 2019-09-01 | |
dc.identifier.citation | Cell death and differentiation, 2019, 26 (9), pp. 1631 - 1645 | |
dc.identifier.issn | 1350-9047 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3064 | |
dc.identifier.eissn | 1476-5403 | |
dc.identifier.doi | 10.1038/s41418-018-0232-2 | |
dc.description.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 drug Phenhydan® as a potent inhibitor of death receptor-induced necroptosis and apoptosis. Accordingly, Phenhydan® blocked activation of necrosome formation/activation as well as death receptor-induced NF-κB signaling by influencing the membrane function of cells, such as lipid raft formation, thus exerting an inhibitory effect on pathophysiologic cell death processes. By targeting death receptor signaling, the already FDA-approved Phenhydan® may provide new therapeutic strategies for inflammation-driven diseases caused by aberrant cell death. | |
dc.format | Print-Electronic | |
dc.format.extent | 1631 - 1645 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | HT29 Cells | |
dc.subject | NIH 3T3 Cells | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Sepsis | |
dc.subject | Multiple Sclerosis | |
dc.subject | Myocardial Infarction | |
dc.subject | Reperfusion Injury | |
dc.subject | Inflammation | |
dc.subject | Phenytoin | |
dc.subject | Anticonvulsants | |
dc.subject | Cell Death | |
dc.subject | Apoptosis | |
dc.subject | Receptor-Interacting Protein Serine-Threonine Kinases | |
dc.subject | Receptors, Death Domain | |
dc.subject | Necroptosis | |
dc.title | The anticonvulsive Phenhydan® suppresses extrinsic cell death. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-10-30 | |
rioxxterms.versionofrecord | 10.1038/s41418-018-0232-2 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell death and differentiation | |
pubs.issue | 9 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
pubs.publication-status | Published | |
pubs.volume | 26 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cell Death and Immunity | |
dc.contributor.icrauthor | Meier, Pascal | |