STING trafficking as a new dimension of immune signaling

The Journal of Experimental Medicine, Год журнала: 2023, Номер 220(3)

Опубликована: Янв. 13, 2023

The cGAS-STING pathway is an evolutionarily conserved immune signaling critical for microbial defense. Unlike other innate pathways that largely rely on stationary cascades of events, STING highly mobile in the cell. activated ER, but only signals after it arrives Golgi, and then quickly degraded by lysosome. Each step trafficking through secretory regulated host factors. Homeostatic via COPI-, COPII-, clathrin-coated vesicles important maintaining baseline tissue cellular immunity. Aberrant vesicular or lysosomal dysfunction produces signal STING, which often leads to pathology mice humans. Many trafficking-mediated diseases appear impact central nervous system, leading neurodegeneration. Therefore, introduces a new dimension likely has broad implications human disease.

Язык: Английский

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Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics

Acta Pharmacologica Sinica, Год журнала: 2023, Номер 44(12), С. 2358 - 2375

Опубликована: Авг. 7, 2023

Язык: Английский

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cGAMP-activated cGAS–STING signaling: its bacterial origins and evolutionary adaptation by metazoans

Nature Structural & Molecular Biology, Год журнала: 2023, Номер 30(3), С. 245 - 260

Опубликована: Март 1, 2023

Язык: Английский

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Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives

Molecular Medicine, Год журнала: 2023, Номер 29(1)

Опубликована: Июль 6, 2023

Abstract The metabolism of glucose and lipids is essential for energy production in the body, dysregulation metabolic pathways these molecules implicated various acute chronic diseases, such as type 2 diabetes, Alzheimer’s disease, atherosclerosis (AS), obesity, tumor, sepsis. Post-translational modifications (PTMs) proteins, which involve addition or removal covalent functional groups, play a crucial role regulating protein structure, localization function, activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, glycosylation. Emerging evidence indicates that are significant modulating lipid by modifying key enzymes proteins. In this review, we summarize current understanding regulatory mechanisms metabolism, with focus on their involvement disease progression associated aberrant metabolism. Furthermore, discuss future prospects PTMs, highlighting potential gaining deeper insights into related diseases.

Язык: Английский

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TAK1 is an essential kinase for STING trafficking

Molecular Cell, Год журнала: 2023, Номер 83(21), С. 3885 - 3903.e5

Опубликована: Окт. 12, 2023

Язык: Английский

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Galectin-9 in cancer therapy: from immune checkpoint ligand to promising therapeutic target

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 11

Опубликована: Янв. 9, 2024

Galectin-9 (Gal-9) is a vital member of the galectin family, functioning as multi-subtype galactose lectin with diverse biological roles. Recent research has revealed that Gal-9’s interaction tumors an independent factor influences tumor progression. Furthermore, Gal-9 in immune microenvironment cross-talks tumor-associated cells, informing clarification identity checkpoint. A thorough investigation into role various cancer types and its could yield novel strategies for subsequent targeted immunotherapy. This review focuses on latest advances understanding direct indirect cross-talk between hematologic malignancies, addition to solid tumors. In addition, we discuss prospects immunotherapy, including ligand TIM-3 potential immune-combination therapy.

Язык: Английский

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Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00536 - e00536

Опубликована: Янв. 1, 2025

Язык: Английский

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Role of AIM2 and cGAS-STING signaling in high fat high carbohydrate diet-induced gut dysbiosis associated neurodegeneration

Life Sciences, Год журнала: 2025, Номер 363, С. 123392 - 123392

Опубликована: Янв. 11, 2025

Язык: Английский

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Regulation and Function of the cGAS-STING Pathway: Mechanisms, Post-Translational Modifications, and Therapeutic Potential in Immunotherapy

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 1721 - 1739

Опубликована: Март 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

Язык: Английский

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Targeting the stimulator of interferon genes (STING) in breast cancer

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Июнь 28, 2023

Breast cancer has a high occurrence rate globally and its treatment demonstrated clinical efficacy with the use of systemic chemotherapy immune checkpoint blockade. Insufficient cytotoxic T lymphocyte infiltration accumulation immunosuppressive cells within tumours are primary factors responsible for inadequate effectiveness breast treatment. The stimulator interferon genes (STING) represents pivotal protein in innate response. Upon activation, STING triggers activation enhancement adaptive functions, resulting therapeutic benefits malignant tumours. signalling pathway is influenced by various such as deoxyribonucleic acid damage response, tumour microenvironment, mitochondrial function. agonists gaining momentum research. This review provides comprehensive overview cyclic guanosine monophosphate-adenosine monophosphate synthase-STING pathway, agonists, latest findings related to their application cancer.

Язык: Английский

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