Cited by 1,062Inflammasome and immune disordersCell death mechanisms and regulationImmune Response and Inflammation

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Pyroptosis versus necroptosis: similarities, differences, and crosstalk

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Frank, Daniel, Vince, James E.·2019·Cell Death & Differentiation

DOI 10.1038/s41418-018-0212-6PMC PMC6294779

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Abstract

Pyroptosis and necroptosis represent two pathways of genetically encoded necrotic cell death. Although these cell death programmes can protect the host against microbial pathogens, their dysregulation has been implicated in a variety of autoimmune and auto-inflammatory conditions. The disease-promoting potential of necroptosis and pyroptosis is likely a consequence of their ability to induce a lytic cell death. This cell suicide mechanism, distinct from apoptosis, allows the release of immunogenic cellular content, including damage-associated molecular patterns (DAMPs), and inflammatory cytokines such as interleukin-1β (IL-1β), to trigger inflammation. In this Review, we discuss recent discoveries that have advanced our understanding on the primary functions of pyroptosis and necroptosis, including evidence for the specific cytokines and DAMPs responsible for driving inflammation. We compare the similar and unique aspects of pyroptotic- and necroptotic-induced membrane damage, and explore how these may functionally impact distinct intracellular organelles and signalling pathways. We also examine studies highlighting the crosstalk that can occur between necroptosis and pyroptosis signalling, and evidence supporting the physiological significance of this convergence. Ultimately, a better understanding of the similarities, unique aspects and crosstalk of pyroptosis and necroptosis will inform as to how these cell death pathways might be manipulated for therapeutic benefit.

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Authors: Frank, D., & Vince, J. E.
Affiliations: The University of Melbourne (AU)
Corresponding author: Vince, James E.
ORCID: Frank, Daniel
Vince, James E.
Venue: Cell Death & Differentiation
Publisher: Springer Science and Business Media LLC
Published: 2018-10-19
Volume: 26
Issue: 1
Pages: 99-114
ISSN: 1350-9047 (ISSN-L)
1476-5403
DOI: 10.1038/s41418-018-0212-6
PMC: PMC6294779
OpenAlex: W2895833591
Cited by: 1,062
References: 170
Citations by year: 2026: 88 · 2025: 142 · 2024: 151 · 2023: 202 · 2022: 237 · 2021: 137 · 2020: 68 · 2019: 34 · 2018: 1
FWCI: 5.91
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Cell Death and Differentiation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Melbourne
National Health and Medical Research Council (1141466)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: pyroptosis, necroptosis, necrosis, damage-associated molecular patterns, IL-1β, inflammation, autoimmune disease, autoinflammation, membrane damage, intracellular signaling
MeSH terms: Alarmins, Pyroptosis, Necroptosis, Gasdermins, Animals, Humans, Inflammation, Necrosis, Protein Kinases, Signal Transduction, Cytokines, Caspase 1, HMGB1 Protein, Phosphate-Binding Proteins, Intracellular Signaling Peptides and Proteins, Inflammasomes

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Pyroptosis versus necroptosis: similarities, differences, and crosstalk

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