Regulation of cGAS–STING signalling and its diversity of cellular outcomes

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

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STING activation and overcoming the challenges associated with STING agonists using ADC (antibody-drug conjugate) and other delivery systems

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111647 - 111647

Published: Feb. 1, 2025

Language: Английский

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cGAS-STING: mechanisms and therapeutic opportunities

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

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Maternal obesity programs cardiac remodeling in offspring via epigenetic, metabolic, and immune dysregulations

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract Maternal obesity during pregnancy significantly increases the offspring’s risk of later-life cardiovascular disease. This study investigated cardiometabolic perturbations by utilizing a mouse model maternal high-fat diet (HFD)-induced that recapitulates metabolic abnormalities observed in humans. We report offspring HFD-fed mothers (Off-HFD) exhibit progression obesity, hypertension, dyslipidemia, and inflexibility when compared with regular diet-fed (Off-RD). Deeper investigation cardiac function further identified significant functional, metabolic, immune adult on HFD. Specifically, Off-HFD mice presented progressing hypertrophy reduced ejection fraction, increased accumulation fibrotic tissue, mitochondrial dysfunction, altered complexity including resident infiltrated macrophages, decreases CD4+ CD8+ T-cell subpopulations. While these alterations may not be immediately catastrophic, they likely predispose to heightened sensitivity nutritional, psychological, or environmental stressors. Analysis DNA methylation hearts newly-weaned from RD HFD revealed numerous differentially methylated CpGs regions within genes associated development, hypertrophy, function, response. Thus, our shows epigenetic remodeling early which is responsible for dysregulation life. These findings uncover potential windows opportunity preventive therapy therapeutic interventions.

Language: Английский

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Maternal Obesity Programs Cardiac Remodeling in Offspring Via Epigenetic, Metabolic, and Immune Dysregulations

Published: Jan. 1, 2025

Language: Английский

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cGAS/STING signalling pathway in senescence and oncogenesis

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 87 - 102

Published: Aug. 31, 2024

Language: Английский

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DNA-sensing pathways in health, autoinflammatory and autoimmune diseases

Nature Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Language: Английский

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Protein-protein interactions in cGAS-STING pathway: a medicinal chemistry perspective

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(17), P. 1801 - 1820

Published: Sept. 1, 2024

Protein-protein interactions (PPIs) play pivotal roles in biological processes and are closely linked with human diseases. Research on small molecule inhibitors targeting PPIs provides valuable insights guidance for novel drug development. The cGAS-STING pathway plays a crucial role regulating innate immunity is implicated various pathological conditions. Therefore, modulators of the have garnered extensive attention. Given that this involves multiple PPIs, modulating associated has emerged as promising strategy pathway. In review, we summarize an overview recent advancements medicinal chemistry into PPI-based propose alternative strategies further discovery based

Language: Английский

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Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA

Amino Acids, Journal Year: 2024, Volume and Issue: 57(1)

Published: Dec. 6, 2024

Abstract Nucleotide-pyrophosphatases/phosphodiesterases (NPP/PDE) are membrane or secreted Zn 2+ -metallohydrolases of nucleoside-5´-monophosphate derivatives. They hydrolyze, for instance, ATP and 4-nitrophenyl-dTMP, belong to the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family that contains seven members (ENPP1-ENPP7). Earlier we had shown an NPP/PDE activity solubilized partially purified from rat liver membranes is inactivated by EDTA in a time-dependent fashion, effect enhanced glycine blocked 4-nitrophenyl-dTMP. Here, extended this observation other free amino acids. Activity assays started after different incubation lengths with provided first-order, apparent inactivation constants (k i(ap) ). With exception cysteine (a strong inhibitor) histidine (itself evoking inactivation), acids themselves did not affect but increased k . The results compatible conformational change evoked interaction enzyme preparation was analyzed identify what ENPP were present. First, hydrolytic on 2´,3´-cGAMP assayed because until very recently ENPP1 only mammalian known display it. hydrolase clearly detected, mass spectrometry data obtained LC-MS/MS gave evidence Enpp3, Enpp4 Enpp5 present low abundance. This finding coincided time recent publication claiming mouse Enpp3 hydrolyzes 2´,3´-cGAMP, Enpp1 account all mice. So, our confirmatory towards 2´,3´-cGAMP. Finally, could be relevant actions dependent protein-protein interactions, like insulin-related effects possibly ENPP3.

Language: Английский

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Free Amino Acids Accelerate the Time-Dependent Inactivation of Rat Liver Nucleotide Pyrophosphatase / Phosphodiesterase Enpp3 elicited by EDTA

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 27, 2024

Abstract Nucleotide-pyrophosphatases/phosphodiesterases (NPP/PDE) are membrane or secreted Zn 2+ -metallohydrolases of nucleoside-5’-monophosphate derivatives. They hydrolyze, for instance, ATP and 4-nitrophenyl-dTMP, belong to the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family that contains seven members (ENPP1-ENPP7). Earlier we had shown an NPP/PDE activity solubilized partially purified from rat liver membranes is inactivated by EDTA in a time-dependent fashion, effect enhanced glycine blocked 4-nitrophenyl-dTMP. Here, extended this observation other free amino acids. Activity assays started after different incubation lengths with provided first-order, apparent inactivation constants (k i(ap) ). With exception cysteine (a strong inhibitor) histidine (itself evoking inactivation), acids themselves did not affect but increased k . The results compatible conformational change evoked interaction enzyme preparation was analyzed identify what ENPP were present. First, hydrolytic on 2’,3’-cGAMP assayed because until very recently ENPP1 only mammalian known display it. hydrolase clearly detected, mass spectrometry data obtained LC-MS/MS gave evidence Enpp3, Enpp4 Enpp5 present low abundance. This finding coincided time recent publication claiming mouse Enpp3 hydrolyzes 2’,3’-cGAMP, Enpp1 account all mice. So, our confirmatory towards 2’,3’-cGAMP. Finally, could be relevant actions dependent protein-protein interactions, like insulin-related effects possibly ENPP3.

Language: Английский

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