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Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target

Necroptosis, or regulated necrosis, is an important type of programmed cell death in addition to apoptosis. Necroptosis induction leads to cell membrane disruption, inflammation and vascularization. It plays important roles in various pathological processes, including neurodegeneration, inflammatory...

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Detalles Bibliográficos
Autores principales: Chen, Jing, Kos, Renate, Garssen, Johan, Redegeld, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952807/
https://www.ncbi.nlm.nih.gov/pubmed/31766571
http://dx.doi.org/10.3390/cells8121486
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author Chen, Jing
Kos, Renate
Garssen, Johan
Redegeld, Frank
author_facet Chen, Jing
Kos, Renate
Garssen, Johan
Redegeld, Frank
author_sort Chen, Jing
collection PubMed
description Necroptosis, or regulated necrosis, is an important type of programmed cell death in addition to apoptosis. Necroptosis induction leads to cell membrane disruption, inflammation and vascularization. It plays important roles in various pathological processes, including neurodegeneration, inflammatory diseases, multiple cancers, and kidney injury. The molecular regulation of necroptotic pathway has been intensively studied in recent years. Necroptosis can be triggered by multiple stimuli and this pathway is regulated through activation of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and pseudokinase mixed lineage kinase domain-like (MLKL). A better understanding of the mechanism of regulation of necroptosis will further aid to the development of novel drugs for necroptosis-associated human diseases. In this review, we focus on new insights in the regulatory machinery of necroptosis. We further discuss the role of necroptosis in different pathologies, its potential as a therapeutic target and the current status of clinical development of drugs interfering in the necroptotic pathway.
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spelling pubmed-69528072020-01-23 Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target Chen, Jing Kos, Renate Garssen, Johan Redegeld, Frank Cells Review Necroptosis, or regulated necrosis, is an important type of programmed cell death in addition to apoptosis. Necroptosis induction leads to cell membrane disruption, inflammation and vascularization. It plays important roles in various pathological processes, including neurodegeneration, inflammatory diseases, multiple cancers, and kidney injury. The molecular regulation of necroptotic pathway has been intensively studied in recent years. Necroptosis can be triggered by multiple stimuli and this pathway is regulated through activation of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and pseudokinase mixed lineage kinase domain-like (MLKL). A better understanding of the mechanism of regulation of necroptosis will further aid to the development of novel drugs for necroptosis-associated human diseases. In this review, we focus on new insights in the regulatory machinery of necroptosis. We further discuss the role of necroptosis in different pathologies, its potential as a therapeutic target and the current status of clinical development of drugs interfering in the necroptotic pathway. MDPI 2019-11-21 /pmc/articles/PMC6952807/ /pubmed/31766571 http://dx.doi.org/10.3390/cells8121486 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chen, Jing
Kos, Renate
Garssen, Johan
Redegeld, Frank
Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target
title Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target
title_full Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target
title_fullStr Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target
title_full_unstemmed Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target
title_short Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target
title_sort molecular insights into the mechanism of necroptosis: the necrosome as a potential therapeutic target
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952807/
https://www.ncbi.nlm.nih.gov/pubmed/31766571
http://dx.doi.org/10.3390/cells8121486
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