PLOS BiologyFeb 24, 2025
ZBP1 initiates RIPK3-mediated #necroptosis during #viral infection in mouse cells, but what about human cells? This study shows that in humans RIPK1 is required for HSV-induced ZBP1-dependent necroptosis; RIPK1's RHIM motif dictates this species difference #plosbiology https://plos.io/3QxqHfe
RIPK1 is required for ZBP1-driven necroptosis in human cells

ZBP1 is known to initiate RIPK3-mediated necroptosis in murine models of viral infection, but how this pathway is regulated in human cells is unclear. This study shows that, unlike in the mouse, RIPK1 is required for HSV-induced ZBP1-dependent necroptosis in human cells; the RHIM motif in RIPK1 dictates this species-specific difference.

Bernhard SchermerMay 21, 2024

📣 A new star is born in the cilia world and cell death galaxy: Emilia Kieckhöfer brilliantly defended her PhD today! Congratulations!!! 🎉🥳👍

#cilia #necroptosis #bbs #raredisease #ciliopathies #celldeath #apoptosis #kidney #cysts #Nphp #Zilien

@cilia
@SFB1403 @CECAD
@UniKoeln

WikiPathwaysDec 9, 2023
Identification of necroptosis-related genes for predicting prognosis and exploring immune infiltration landscape in colon adenocarcinoma. https://doi.org/10.3389/fonc.2022.941156 #Tcga #Necroptosis #ColonAdenocarcinoma #PrognosisModel #Immune
Identification of necroptosis-related genes for predicting prognosis and exploring immune infiltration landscape in colon adenocarcinoma

BackgroundNecroptosis is a recently discovered form of cell death that plays an important role in the occurrence and development of colon adenocarcinoma (COAD). Our study aimed to construct a risk score model to predict the prognosis of patients with COAD based on necroptosis-related genes.MethodsThe gene expression data of COAD and normal colon samples were obtained from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to calculate the risk score based on prognostic necroptosis-related differentially expressed genes (DEGs). Based on the risk score, patients were classified into high- and low-risk groups. Then, nomogram models were built based on the risk score and clinicopathological features. Otherwise, the model was verified in the Gene Expression Omnibus (GEO) database. Additionally, the tumor microenvironment (TME) and the level of immune infiltration were evaluated by “ESTIMATE” and single-sample gene set enrichment analysis (ssGSEA). Functional enrichment analysis was carried out to explore the potential mechanism of necroptosis in COAD. Finally, the effect of necroptosis on colon cancer cells was explored through CCK8 and transwell assays. The expression of necroptosis-related genes in colon tissues and cells treated with necroptotic inducers (TNFα) and inhibitors (NEC-1) was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR).Result...

Frontiers
Alexey VeraksaSep 15, 2023
Cool story: xenografting of human #neurons into mouse #Alzheimers model resulted in their death by #necroptosis. This process involves #lncRNA MEG3, possibly via TNF inflammatory signaling. This study revealed human-specific vulnerability in AD.
#neuroscience
https://www.science.org/doi/10.1126/science.abp9556
Marek Pavliš 🇨🇿 🇪🇺Sep 15, 2023

🧠 "For the first time we get a clue to how and why neurons die in #Alzheimer's disease...

They say abnormal amyloid starts to build up in the spaces between #neurons, leading to brain #inflammation, which the neurons do not like...

Tangles of tau appear and the brain #cells start producing a specific molecule (MEG3) that triggers death by #necroptosis.

The brain cells survived when the team were able to block MEG3."

👉 https://www.bbc.com/news/health-66816268

Scientists discover how brain cells die in Alzheimer’s

The findings, which had been a mystery for decades, give new ideas for treating the disease.

BBC News
Brent StockwellAug 17, 2023
My thoughts on why the field of #celldeath writ large is poised to yield big breakthroughs in #health and #medicine -- driven by advances in #necroptosis, #pyroptosis and #ferroptosis
https://medium.com/wise-well/life-saving-cures-emerge-as-mysteries-of-cell-death-are-solved-24a06fac98bb
Giuseppe MichieliMar 4, 2023
The Defenders of the #Alveolus Succumb in #COVID19 #Pneumonia to #SARS-CoV-2 and #Necroptosis, Pyroptosis and Panoptosis https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad056/7068922?rss=1
Phys.orgDec 9, 2022

Referenced link: https://phys.org/news/2022-12-fret-based-biosensor-visualizes-necroptosis-vivo.html
Discuss on https://discu.eu/q/https://phys.org/news/2022-12-fret-based-biosensor-visualizes-necroptosis-vivo.html

Originally posted by Phys.org / @[email protected]: https://twitter.com/physorg_com/status/1601227430320082946#m

FRET-based biosensor visualizes execution of #necroptosis in vivo @CommsBio @NatureComms https://www.nature.com/articles/s42003-022-04300-0 https://phys.org/news/2022-12-fret-based-biosensor-visualizes-necroptosis-vivo.html

FRET-based biosensor visualizes execution of necroptosis in vivo

Necroptosis is a form of regulated cell death (RCD) similar to apoptosis, the most commonly studied type of RCD. In contrast to apoptosis, plasma membrane rupture in necroptotic cells occurs at early time points. For this reason, scientists think that necroptosis elicits strong inflammation in surrounding tissues and plays a role in inflammation-associated diseases. However, it is not well understood where and when necroptosis occurs in physiological and pathological conditions in vivo.

Phys.org
Bischöfliche MarienschuleDec 3, 2022

Wir freuen uns sehr für unseren Kooperationspartner Bernhard Schermer @cilib über die Veröffentlichung (Open Access!) einer Arbeit zur Rolle von Cilien auf der Zelloberfläche von Nierenzellen und der Zelltodreaktion. Damit kann eine bestimmte, vererbte Nierenkrankheit wieder eine Stück besser verstanden werden. Herzlichen Glückwunsch! 🎉🎉👍👍

👉 https://www.nature.com/articles/s41420-022-01272-2​

#cilia #CellDeath @cilia
#necroptosis #UniklinikKöln @CECAD
@UniKoeln​

Primary cilia suppress Ripk3-mediated necroptosis - Cell Death Discovery

Cilia are sensory organelles that project from the surface of almost all cells. Nephronophthisis (NPH) and NPH-related ciliopathies are degenerative genetic diseases caused by mutation of cilia-associated genes. These kidney disorders are characterized by progressive loss of functional tubular epithelial cells which is associated with inflammation, progressive fibrosis, and cyst formation, ultimately leading to end-stage renal disease. However, disease mechanisms remain poorly understood. Here, we show that targeted deletion of cilia in renal epithelial cells enhanced susceptibility to necroptotic cell death under inflammatory conditions. Treatment of non-ciliated cells with tumor necrosis factor (TNF) α and the SMAC mimetic birinapant resulted in Ripk1-dependent cell death, while viability of ciliated cells was almost not affected. Cell death could be enhanced and shifted toward necroptosis by the caspase inhibitor emricasan, which could be blocked by inhibitors of Ripk1 and Ripk3. Moreover, combined treatment of ciliated and non-ciliated cells with TNFα and cycloheximide induced a cell death response that could be partially rescued with emricasan in ciliated cells. In contrast, non-ciliated cells responded with pronounced cell death that was blocked by necroptosis inhibitors. Consistently, combined treatment with interferon-γ and emricasan induced cell death only in non-ciliated cells. Mechanistically, enhanced necroptosis induced by loss of cilia could be explained by induction of Ripk3 and increased abundance of autophagy components, including p62 and LC3 associated with the Ripk1/Ripk3 necrosome. Genetic ablation of cilia in renal tubular epithelial cells in mice resulted in TUNEL positivity and increased expression of Ripk3 in kidney tissue. Moreover, loss of Nphp1, the most frequent cause of NPH, further increased susceptibility to necroptosis in non-ciliated epithelial cells, suggesting that necroptosis might contribute to the pathogenesis of the disease. Together, these data provide a link between cilia-related signaling and cell death responses and shed new light on the disease pathogenesis of NPH-related ciliopathies.

Nature
SFB1403Dec 2, 2022
📢 Paper Alert 📢 Check out the new publication by @[email protected] and his Team in which they report that #PrimaryCilia suppress #Ripk3-mediated #necroptosis. Congratulations to this great work within the #sfb1403 🎉☠️➡️ https://www.nature.com/articles/s41420-022-01272-2
Primary cilia suppress Ripk3-mediated necroptosis - Cell Death Discovery

Cilia are sensory organelles that project from the surface of almost all cells. Nephronophthisis (NPH) and NPH-related ciliopathies are degenerative genetic diseases caused by mutation of cilia-associated genes. These kidney disorders are characterized by progressive loss of functional tubular epithelial cells which is associated with inflammation, progressive fibrosis, and cyst formation, ultimately leading to end-stage renal disease. However, disease mechanisms remain poorly understood. Here, we show that targeted deletion of cilia in renal epithelial cells enhanced susceptibility to necroptotic cell death under inflammatory conditions. Treatment of non-ciliated cells with tumor necrosis factor (TNF) α and the SMAC mimetic birinapant resulted in Ripk1-dependent cell death, while viability of ciliated cells was almost not affected. Cell death could be enhanced and shifted toward necroptosis by the caspase inhibitor emricasan, which could be blocked by inhibitors of Ripk1 and Ripk3. Moreover, combined treatment of ciliated and non-ciliated cells with TNFα and cycloheximide induced a cell death response that could be partially rescued with emricasan in ciliated cells. In contrast, non-ciliated cells responded with pronounced cell death that was blocked by necroptosis inhibitors. Consistently, combined treatment with interferon-γ and emricasan induced cell death only in non-ciliated cells. Mechanistically, enhanced necroptosis induced by loss of cilia could be explained by induction of Ripk3 and increased abundance of autophagy components, including p62 and LC3 associated with the Ripk1/Ripk3 necrosome. Genetic ablation of cilia in renal tubular epithelial cells in mice resulted in TUNEL positivity and increased expression of Ripk3 in kidney tissue. Moreover, loss of Nphp1, the most frequent cause of NPH, further increased susceptibility to necroptosis in non-ciliated epithelial cells, suggesting that necroptosis might contribute to the pathogenesis of the disease. Together, these data provide a link between cilia-related signaling and cell death responses and shed new light on the disease pathogenesis of NPH-related ciliopathies.

Nature