STING agonist 8803 reprograms the immune microenvironment and increases survival in preclinical models of glioblastoma

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(12)

Published: June 16, 2024

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and Ivy Glioblastoma Atlas, expression was found in myeloid populations perivascular space. The agonist 8803 increased median survival multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% mice were cured. Ex vivo flow cytometry profiling during therapeutic window demonstrated increases trafficking activation, alongside enhancement CD8+ T cell NK effector responses. Treatment with reprogrammed microglia express costimulatory CD80/CD86 iNOS, while decreasing immunosuppressive CD206 arginase. In humanized mice, is epigenetically silenced, activity maintained, further attesting dependency reprogramming. Although combination a STAT3 inhibitor did not enhance activity, addition anti-PD-1 antibodies treatment enhanced blockade-responsive glioma model. summary, as monotherapy demonstrates marked meriting consideration for clinical translation.

Language: Английский

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cGAS-STING targeting offers novel therapeutic opportunities in neurological diseases

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 105, P. 102691 - 102691

Published: Feb. 13, 2025

Language: Английский

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Interleukin-6 deficiency reduces neuroinflammation by inhibiting the STAT3-cGAS-STING pathway in Alzheimer’s disease mice

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 1, 2024

The Interleukin-6 (IL-6)-signal transducer and activator of transcription 3 (STAT3) pathway, along with the cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) are critical contributors to neuroinflammation in Alzheimer's disease (AD). Although previous research outside context AD has indicated that IL-6-STAT3 pathway may regulate cGAS-STING exact molecular mechanisms through which influences still not well understood.

Language: Английский

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The impact of neuroinflammation on neuronal integrity

Immunological Reviews, Journal Year: 2024, Volume and Issue: 327(1), P. 8 - 32

Published: Oct. 1, 2024

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, disease pathologies. However, dysregulation of neuroinflammatory response could significantly affect neurons terms function structure, leading profound health implications. Although tremendous progress has been made understanding relationship between processes alterations neuronal integrity, specific implications concerning both structure have not extensively covered, with exception perspectives on glial activation neurodegeneration. Thus, this review aims provide comprehensive overview multifaceted interactions key inflammatory players, exploring mechanisms through which inflammation influences functionality structural integrity CNS. Further, it will discuss how these lead impairment functions architecture highlight consequences caused dysregulated functions, such as cognitive dysfunction mood disorders. By integrating insights from recent research findings, enhance our landscape set stage for future interventions that transform current approaches preserve CNS-related conditions.

Language: Английский

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hESC-derived extracellular vesicles enriched with MFGE-8 and the GSH redox system act as senotherapeutics for neural stem cells in ischemic stroke

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Senescence as a Molecular Target in Skin Aging and Disease

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102686 - 102686

Published: Feb. 1, 2025

Language: Английский

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Investigating the Potential Therapeutic Targeting of the JAK-STAT Pathway in Cerebrovascular Diseases: Opportunities and Challenges

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

Published: March 18, 2025

Language: Английский

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Artesunate demonstrates neuroprotective effect through activation of lysosomal function and inhibition of cGAS-STING pathway

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110426 - 110426

Published: March 1, 2025

Language: Английский

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Hydroxysafflower yellow A alleviates the inflammatory response in astrocytes following cerebral ischemia by inhibiting the LCN2/STAT3 feedback loop

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(4)

Published: March 26, 2025

Language: Английский

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The STING Signaling: A Novel Target for Central Nervous System Diseases

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: April 7, 2025

The canonical cyclic GMP-AMP (cGAMP) synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway has been widely recognized as a crucial mediator inflammation in many diseases, including tumors, infections, and tissue damage. STING signaling can also be activated cGAS- or cGAMP-independent manner, although the specific mechanisms remain unclear. In-depth studies on structural molecular biology have led to development therapeutic strategies involving modulators their targeted delivery. These may effectively penetrate blood-brain barrier (BBB) target multiple central nervous system (CNS) diseases humans. In this review, we outline both non-canonical pathways activation describe general associations between activity CNS diseases. Finally, discuss prospects for delivery clinical application agonists inhibitors, highlighting novel

Language: Английский

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