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dc.contributor.authorRiebeling, T
dc.contributor.authorJamal, K
dc.contributor.authorWilson, R
dc.contributor.authorKolbrink, B
dc.contributor.authorvon Samson-Himmelstjerna, FA
dc.contributor.authorMoerke, C
dc.contributor.authorRamos Garcia, L
dc.contributor.authorDahlke, E
dc.contributor.authorMichels, F
dc.contributor.authorLühder, F
dc.contributor.authorSchunk, D
dc.contributor.authorDoldi, P
dc.contributor.authorTyczynski, B
dc.contributor.authorKribben, A
dc.contributor.authorFlüh, C
dc.contributor.authorTheilig, F
dc.contributor.authorKunzendorf, U
dc.contributor.authorMeier, P
dc.contributor.authorKrautwald, S
dc.date.accessioned2021-01-25T15:17:36Z
dc.date.issued2020-12-03
dc.identifier.citationCell death and differentiation, 2020
dc.identifier.issn1350-9047
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4316
dc.identifier.eissn1476-5403
dc.identifier.doi10.1038/s41418-020-00690-y
dc.description.abstractThe receptor-interacting serine/threonine protein kinase 1 (RIPK1) is a key mediator of regulated cell death and inflammation. Recent studies suggest that RIPK1 inhibition would fundamentally improve the therapy of RIPK1-dependent organ damage in stroke, myocardial infarction, kidney failure, and systemic inflammatory response syndrome. Additionally, it could ameliorate or prevent multi-organ failure induced by cytokine release in the context of hyperinflammation, as seen in COVID-19 patients. Therefore, we searched for a RIPK1 inhibitor and present the aromatic antiepileptic and FDA-approved drug primidone (Liskantin®) as a potent inhibitor of RIPK1 activation in vitro and in a murine model of TNFα-induced shock, which mimics the hyperinflammatory state of cytokine release syndrome. Furthermore, we detected for the first time RIPK1 activation in the respiratory tract epithelium of hospitalized patients who tested positive for SARS-CoV-2 infection. Our data provide a strong rationale for evaluating the drug primidone in conditions of hyperinflammation in humans.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePrimidone blocks RIPK1-driven cell death and inflammation.
dc.typeJournal Article
dcterms.dateAccepted2020-11-17
rioxxterms.versionofrecord10.1038/s41418-020-00690-y
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-12-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell death and differentiation
pubs.notesNot 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-statusPublished
pubs.embargo.termsNot known
icr.researchteamCell Death and Immunityen_US
dc.contributor.icrauthorMeier, Pascalen


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