Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases.
MLKL
RIPK3
caspase 8
inflammatory bowel disease
necroptosis
therapeutic
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
11
04
2023
accepted:
07
06
2023
medline:
7
7
2023
pubmed:
6
7
2023
entrez:
6
7
2023
Statut:
epublish
Résumé
A delicate balance between programmed cell death and proliferation of intestinal epithelial cells (IEC) exists in the gut to maintain homeostasis. Homeostatic cell death programs such as anoikis and apoptosis ensure the replacement of dead epithelia without overt immune activation. In infectious and chronic inflammatory diseases of the gut, this balance is invariably disturbed by increased levels of pathologic cell death. Pathological forms of cell death such as necroptosis trigger immune activation barrier dysfunction, and perpetuation of inflammation. A leaky and inflamed gut can thus become a cause of persistent low-grade inflammation and cell death in other organs of the gastrointestinal (GI) tract, such as the liver and the pancreas. In this review, we focus on the advances in the molecular and cellular understanding of programmed necrosis (necroptosis) in tissues of the GI tract. In this review, we will first introduce the reader to the basic molecular aspects of the necroptosis machinery and discuss the pathways leading to necroptosis in the GI system. We then highlight the clinical significance of the preclinical findings and finally evaluate the different therapeutic approaches that attempt to target necroptosis against various GI diseases. Finally, we review the recent advances in understanding the biological functions of the molecules involved in necroptosis and the potential side effects that may occur due to their systemic inhibition. This review is intended to introduce the reader to the core concepts of pathological necroptotic cell death, the signaling pathways involved, its immuno-pathological implications, and its relevance to GI diseases. Further advances in our ability to control the extent of pathological necroptosis will provide better therapeutic opportunities against currently intractable GI and other diseases.
Identifiants
pubmed: 37409125
doi: 10.3389/fimmu.2023.1203903
pmc: PMC10318896
doi:
Substances chimiques
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1203903Informations de copyright
Copyright © 2023 Patankar, Bubeck, Acera and Becker.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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