The cGAS-STING pathway in ischemia-reperfusion injury in acute cerebral infarction: a new therapeutic opportunities? DOI Creative Commons
Jun Hu,

Mengxiang Tian

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 17, 2024

The innate immune response is the body's first line of defense against external pathogens and endogenous damage signals. cGAS-STING pathway a crucial component response, playing key role in initiating antiviral anti-infective responses by recognizing cytosolic DNA. Acute cerebral infarction one leading causes death disability worldwide, with primary treatment approach being restoration blood flow to ischemic brain tissue. However, reperfusion injury remains significant challenge during treatment. overactivation its association ischemia-reperfusion have been confirmed numerous studies. This article will systematically elucidate mechanisms pathway, acute infarction, current research status inhibitors, application nanomaterials this context, evaluating therapeutic potential pathway.

Language: Английский

Liver‐Secreted Extracellular Vesicles Promote Cirrhosis‐Associated Skeletal Muscle Injury Through mtDNA‐cGAS/STING Axis DOI Creative Commons
Xiaoli Fan, Yunke Peng, Bo Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Skeletal muscle atrophy (sarcopenia) is a serious complication of liver cirrhosis, and chronic inflammation plays pivotal role in its pathologenesis. However, the detailed mechanism through which injured tissues mediate skeletal inflammatory injury remains elusive. Here, it reported that hepatocytes might secrete mtDNA‐enriched extracellular vesicles (EVs) to trigger by activating cGAS‐STING pathway. Briefly, secreted increased amounts EVs into circulation, are then engulfed primarily macrophages subsequently induce signaling its‐mediated response muscles. In contrast, suppression hepatic EV secretion or STING significantly alleviated cirrhosis‐induced vivo. Circulating from cirrhotic patients showed higher levels mtDNA, EV‐mtDNA positively correlated with severity injury. hepatocytes, mitochondrial damage promoted release cytosolic mtDNA subsequent EVs. This study reveals hepatocyte‐derived via mtDNA‒STING axis, while targeted blockade represents potential therapeutic approach for preventing cirrhosis‐associated atrophy.

Language: Английский

Citations

1
Pathophysiology of IBD as a Key Strategy for Polymeric Nanoparticle Development DOI Creative Commons

Elena Gardey,

Johannes C. Brendel, Andreas Stallmach

et al.

Advanced Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal (GI) tract with an uncertain etiology. Currently, IBD therapy relies on induction clinical remission followed by maintenance using anti‐inflammatory drugs and immunosuppressants; however, definite cure still out scope. Established approaches are characterized adverse drug‐related side effects that can even be potentially life‐threatening. In contrast, increased interest remarkable scientific progress in targeted drug delivery systems offer promising approach to reduce systemic events, delivering therapeutic substances only inflamed tissue. All alteration barrier integrity, especially disturbed epithelial barrier, unique pattern receptors cell surface and/or oxidative stress milieu areas used as effective for controlled delivery. Hence, this review focuses pathophysiology GI potential strategy polymeric nanoparticles treatment. Interdisciplinary efforts between chemistry gastroenterology/immunology promise create novel synergies improve development nanoparticle significant impact. regard, current challenges translation nanomedicine also discussed.

Language: Английский

Citations

0
Orally Bioavailable and Site-Selective Covalent STING Inhibitor Derived from a Macrocyclic Marine Diterpenoid DOI Creative Commons
Guang‐Hao Niu,

Wan‐Chi Hsiao,

Po-Hsun Lee

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Pharmacological inhibition of the cGAS-STING-controlled innate immune pathway is an emerging therapeutic strategy for a myriad inflammatory diseases. Here, we report GHN105 as orally bioavailable covalent STING inhibitor. Late-stage diversification briarane-type diterpenoid excavatolide B allowed installation solubility-enhancing functional groups while enhancing its activity inhibitor against multiple human variants, including S154 variant responsible genetic autoimmune disease. Selectively engaging membrane-proximal Cys91 residue STING, dose-dependently inhibited cGAS-STING signaling and type I interferon responses in cells vivo. Moreover, administered exhibited on-target engagement vivo markedly reversed key pathological features delayed treatment acute colitis mouse model. Our study provided proof concept that synthetic briarane analog serves safe, site-selective, active devises regimen allows long-term systemic administration.

Language: Английский

Citations

0
Oral Lipid-Based Nanomedicine for the Inhibition of the cGAS-STING Pathway in Inflammatory Bowel Disease Treatment DOI Creative Commons
Léo Guilbaud, Cheng Chen, Inês Domingues

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Harnessing the effect of cyclic GMP-AMP Synthase-STimulator INterferon Genes (cGAS-STING) signaling pathway has emerged as a promising approach to developing novel strategies for oral treatment inflammatory bowel disease (IBD). In this work, we screened different cGAS-STING inhibitors in vitro murine macrophages. Then, encapsulated inhibitor H-151 within lipid nanocapsules (LNCs), owing their inherent ability induce secretion glucagon-like peptide 2 (GLP-2), re-epithelizing peptide, upon administration. We demonstrated that our formulation (LNC(H-151)) could GLP-2 and selectively target its downstream key markers (including TBK1 pTBK1) while reducing expression pro-inflammatory cytokines associated with (TNF-α CXCL10) an vivo acute dextran sodium sulfate (DSS)-induced colitis mouse model, administration LNC(H-151) significantly reduced levels comparable CTRL Healthy group promoting mucosal healing. The therapeutic potential scalable cost-effective nanomedicine warrants further investigation alternative IBD.

Language: Английский

Citations

0
Nano-Delivery of STING Agonists: Unraveling the Potential of Immunotherapy DOI
Meng Zhang,

Yating Ji,

Mingxia Liu

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Tea residue protein-derived oligopeptides attenuate DSS-induced acute colitis complicated with hepatic injury in C57BL/6J mice by regulating the gut-microbiome-liver axis DOI

Fengxue Qi,

Ziyi Shen,

Simeng Zhou

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156792 - 156792

Published: April 22, 2025

Language: Английский

Citations

0
Macrophage targeting precision nanomedicine utilizing ROS-responsive metallozyme-loaded nanomicelle for enhanced treatment of gout-induced inflammation DOI Creative Commons

Padmanaban Sathiyamoorthy,

Shyam Vasvani, Sree Samanvitha Kuppa

et al.

Science and Technology of Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

Citations

0
Reactive Oxygen Species-Responsive Polymer Drug Delivery System Targeted Oxidative Stressed Colon Cells to Ameliorate Colitis DOI

Wo-Qi Cai,

Wanqi Liang, Dong Li

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Ulcerative colitis (UC) is a chronic inflammatory condition that imposes huge healthcare burden globally. The inflamed colon marked by an abundance of positively charged proteins, increased reactive oxygen species (ROS), disrupted intestinal barrier, and imbalanced gut microbiome. Leveraging these features, we designed negatively ROS-responsive nanocarrier using diselenide-bond-modified carboxymethyl cellulose (CMC) for the targeted delivery curcumin, natural ROS-scavenging antioxidant, to treat UC. design rationale encompasses three key aspects: (1) biocompatible biodegradable CMC matrix stabilizes curcumin during digestion; (2) diselenide bonds enable redox-triggered release at sites, ensuring precise therapeutic action; (3) negative charge nanoparticles enhances interactions with proteins in tissues, improving site-specific accumulation. Experimental validation confirmed principles, demonstrating resulting effectively preserve digestion sites. Additionally, interact folic acid receptors (positively proteins) are overexpressed on oxidatively stressed cell membranes, leading specific accumulation tissue. Subsequently, scavenge excessive ROS, restore barrier function, modulate microbiota. These synergistic actions collectively contribute significant mitigation symptoms both preventive regimens, suggesting promising alternative approach

Language: Английский

Citations

0
cGAS-STING DNA-sensing in inflammatory bowel diseases DOI

Georges Dimitrov,

Bernhard Ryffel, Dieudonnée Togbe

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

3
Regulation and Function of the cGAS-STING Pathway: Mechanisms, Post-Translational Modifications, and Therapeutic Potential in Immunotherapy DOI Creative Commons
Yuhan Chen, Shi‐Jun Yue, Lingyan Yu

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1721 - 1739

Published: March 1, 2025

Abstract: Autoimmune diseases arise when the immune system attacks healthy tissues, losing tolerance for self-tissues. Normally, recognizes and defends against pathogens like bacteria viruses. The cGAS-STING pathway, activated by pattern-recognition receptors (PRRs), plays a key role in autoimmune responses. cGAS protein senses pathogenic DNA synthesizes cGAMP, which induces conformational changes STING, activating kinases IKK TBK1 leading to expression of interferon genes or inflammatory mediators. This pathway is crucial immunotherapy, innate immunity, enhancing antigen presentation, modulating tumor microenvironment, integrating into therapeutic strategies. Modulation strategies include small molecule inhibitors, oligonucleotide therapies, antibody genetic epigenetic regulation, cytokine metabolite modulation, nanoscale delivery systems. Post-translational modifications (PTMs) such as phosphorylation, acetylation, ubiquitination, methylation, palmitoylation, glycosylation, fine-tune responses regulating activity, stability, localization, interactions. These are interconnected collectively influence functionality. We summarize functions its PTMs non-immune cells across various diseases, explore potential clinical applications. Keywords: cGAS, post-transcriptional regulation

Language: Английский

Citations

0