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The role of regulated necrosis in endocrine diseases

Research output: Contribution to journalReview articlepeer-review

Wulf Tonnus, Alexia Belavgeni, Felix Beuschlein, Graeme Eisenhofer, Martin Fassnacht, Matthias Kroiss, Nils P. Krone, Martin Reincke, Stefan R. Bornstein, Andreas Linkermann

Original languageEnglish
Pages (from-to)497-510
Number of pages14
JournalNature Reviews Endocrinology
Volume17
Issue number8
DOIs
Accepted/In press2021
PublishedAug 2021

Bibliographical note

Funding Information: A.L. is supported by a Heisenberg-Professorship granted by the German Research Foundation (DFG), project number 324141047. Work in the Linkermann Lab and the Bornstein Lab is funded by Medical Clinic 3, University Hospital Carl Gustav Carus Dresden, Germany, and supported by the SFB-TRR 205, SFB-TRR 127 and the international research training group (IRTG) 2251. This work was further supported by the transCampus to S.R.B. and A.L.. N.P.K. was supported by the DFG, project KR3363/3-1. F.B. is supported by the Hochschulmedizin Zürich through the Flagship project Immuno-TarGET. We would like to thank all members of the Linkermann Lab for the ongoing discussions. We cordially thank R. Drtina for her assistance with preparing the first draft of the manuscript. Publisher Copyright: © 2021, Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

The death of endocrine cells is involved in type 1 diabetes mellitus, autoimmunity, adrenopause and hypogonadotropism. Insights from research on basic cell death have revealed that most pathophysiologically important cell death is necrotic in nature, whereas regular metabolism is maintained by apoptosis programmes. Necrosis is defined as cell death by plasma membrane rupture, which allows the release of damage-associated molecular patterns that trigger an immune response referred to as necroinflammation. Regulated necrosis comes in different forms, such as necroptosis, pyroptosis and ferroptosis. In this Perspective, with a focus on the endocrine environment, we introduce these cell death pathways and discuss the specific consequences of regulated necrosis. Given that clinical trials of necrostatins for the treatment of autoimmune conditions have already been initiated, we highlight the therapeutic potential of such novel therapeutic approaches that, in our opinion, should be tested in endocrine disorders in the future.

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