RIPK1 is known as a driver of cell death and inflammation. In this issue of Immunity, Imai et al. and Mannion et al. find that these same processes are also induced by RIPK1 inactivation and highlight the therapeutic potential of RIPK1 elimination.
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http://dx.doi.org/10.1016/j.immuni.2024.06.002 | DOI Listing |
Cell Mol Biol (Noisy-le-grand)
January 2025
Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Türkiye.
Increasing evidence suggests that inhibition of receptor-interacting serine/threonine-protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like pseudokinase (MLKL) necrosome has protective effects in vivo models of painful conditions seen in humans associated with inflammation and demyelination in the central nervous system. However, the contribution of RIPK1-driven necroptosis to inflammatory pain remains unknown. Therefore, this study aims to determine the effect of necrostatin (Nec) -1s, a selective RIPK1 inhibitor, on lipopolysaccharide (LPS)-induced inflammatory pain and related underlying mechanisms.
View Article and Find Full Text PDFRespir Investig
January 2025
Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, China. Electronic address:
Background: The mechanism underlying necroptosis in pulmonary vessel endothelial cells (PVECs) resulting from long non-coding RNA (lncRNA)-induced alternative splicing (AS) of target genes in acute lung injury (ALI) remains unclear.
Methods: Lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and lncRNAs was analyzed via RT-PCR in PVECs. Full-transcriptome sequencing was used to detect AS-related mRNAs.
PLoS One
January 2025
Michael Sayegh Faculty of Pharmacy, Aqaba University of Technology, Aqaba, Jordan.
Breast cancer remains a significant challenge in oncology, highlighting the need for alternative therapeutic strategies that target necroptosis to overcome resistance to conventional therapies. Recent investigations into natural compounds have identified 8,12-dimethoxysanguinarine (SG-A) from Eomecon chionantha as a potential necroptosis inducer. This study presents the first computational exploration of SG-A interactions with key necroptotic proteins-RIPK1, RIPK3, and MLKL-through molecular docking, molecular dynamics (MD), density functional theory (DFT), and molecular electrostatic potential (MEP) analyses.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Jacaranone derived from , a traditional Chinese medicine used for centuries, has been documented to exhibit anti-inflammatory and antiproliferative properties in various tumor cell lines. However, the mechanism of action and relationship between inflammation and apoptosis induced by jacaranone remain inadequately elucidated. In this study, the targets of jacaranone and cancer were identified from various databases, while potential targets and pathways were predicted through the analysis of the protein-protein interactions (PPI) network and pathway enrichment.
View Article and Find Full Text PDFCells
December 2024
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
Functional cell death pathways are essential for normal ocular vascular development and tissue homeostasis. As our understanding of necrosis-based cell death pathways has expanded, the inclusion of regulated forms, including necroptosis, ferroptosis, and oxytosis, has occurred. Although the existence of these pathways is well described, our understanding of their role during vascular development and pathological neovascularization is very limited.
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