Relationship between the cGAS−STING and NF-κB pathways-role in neurotoxicity

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116698 - 116698

Published: May 6, 2024

Neurotoxicity can cause a range of symptoms and disorders in humans, including neurodegenerative diseases, neurodevelopmental disorders, nerve conduction abnormalities, neuroinflammation, autoimmune cognitive deficits. The cyclic guanosine-adenosine synthase (cGAS)-stimulator interferon genes (STING) pathway NF-κB are two important signaling pathways involved the innate immune response. cGAS-STING is activated by recognition intracellular DNA, which triggers production type I interferons pro-inflammatory cytokines, such as tumor necrosis factor, IL-1β, IL-6. These cytokines play role oxidative stress mitochondrial dysfunction neurons. various stimuli, bacterial lipopolysaccharide, viral particle components, neurotoxins. activation may lead to promote neuroinflammation neuronal damage. A potential interaction exists between pathways, blocks STING degradation inhibiting microtubule-mediated transport. This review examines progress research on roles these neurotoxicity their interrelationships. Understanding mechanisms will provide valuable therapeutic insights for preventing controlling neurotoxicity.

Language: Английский

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Gut Microbiota Metabolites Mediate Bax to Reduce Neuronal Apoptosis via cGAS/STING Axis in Epilepsy

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(12), P. 9794 - 9809

Published: Aug. 22, 2023

Language: Английский

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HIV-1 Vpu and SARS-CoV-2 ORF3a proteins disrupt STING-mediated activation of antiviral NF-κB signaling

Science Signaling, Journal Year: 2025, Volume and Issue: 18(870)

Published: Jan. 21, 2025

Activation of the stimulator interferon genes (STING) pathway by cytosolic DNA leads to activation transcription factors regulatory factor 3 (IRF3) and nuclear κB (NF-κB). Although many viruses produce proteins that inhibit IRF3-dependent antiviral responses, some STING-induced NF-κB without blocking IRF3 activation. Here, we found STING-activated, NF-κB–dependent, IRF3-independent innate immunity inhibited replication virus herpes simplex type 1 (HSV-1), RNA coxsackievirus A16 (CV-A16), retrovirus HIV-1. The HIV-1 nonstructural protein Vpu bound STING prevented it from interacting with upstream kinase inhibitor subunit β (IKKβ), thus signaling. This function was conserved among diverse simian immunodeficiency strains distinct its action in disrupting other host pathways. Furthermore, ORF3a coronavirus SARS-CoV-2 also promoted viral activity but not IRF3. These findings demonstrate have convergently evolved selectively NF-κB–mediated downstream activation, suggesting targeting this may represent a promising strategy.

Language: Английский

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Hypermethylation of the glutathione peroxidase 4 gene promoter is associated with the occurrence of immune tolerance phase in chronic hepatitis B

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

Published: March 21, 2024

Abstract Background Hepatitis B virus (HBV) infection is a public health problem that seriously threatens human health. This study aimed to investigate the clinical significance of glutathione peroxidase 4(GPX4) in occurrence and development chronic hepatitis (CHB). Methods A total 169 participants including 137 patients with CHB 32 healthy controls (HCs) were recruited. We detected expression GPX4 stimulator interferon genes ( STING) peripheral blood mononuclear cells (PBMCs) by real-time quantitative polymerase chain reaction (RT-qPCR). The methylation level gene promoter PBMCs was TaqMan probe-based methylation-specific PCR (MethyLight). Enzyme-linked immunosorbent assay (ELISA) performed detect serum levels GPX4, IFN-β, oxidative stress (OS) related molecules, pro-inflammatory cytokines. Results lower than those HCs, but higher especially at immune tolerance phase. STING mRNA IFN-β activation phase reactivation other phases HCs. from had certain correlation levels. In addition, correlated molecules associated OS inflammation. Conclusions may play an important role pathogenesis CHB, which provide new ideas for functional cure CHB.

Language: Английский

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A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: July 13, 2024

Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit greater array non-structural compared to low-pathogenic strains, facilitating their ability induce via multiple pathways. Moreover, these are adept at dampening host immune responses, thereby bolstering replication persistence. This review delves into intricate interplay between apoptosis, systematically elucidating molecular mechanisms underpinning induction by proteins. Furthermore, it explores potential therapeutic avenues stemming from inhibition antiviral agents utilization apoptosis-inducing modalities. These insights not only shed light on pathogenesis but also offer novel perspectives cancer therapy.

Language: Английский

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SARS‐CoV‐2, HIV, and HPV: Convergent evolution of selective regulation of cGAS–STING signaling

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Oct. 14, 2022

Abstract Recognizing aberrant cytoplasmic double‐stranded DNA and stimulating innate immunity is essential for the host's defense against viruses tumors. Cyclic GMP–AMP (cGAMP) synthase (cGAS) a cytosolic sensor that synthesizes second messenger 2′3′‐cGAMP subsequently activates stimulator of interferon genes (STING)‐mediated activation TANK‐binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) production type I (IFN‐I). Both cGAS–STING‐mediated IFN‐I antiviral countermeasures developed by diverse have been extensively studied. However, recent studies revealed convergent evolutionary feature severe acute respiratory syndrome coronavirus 2 human immunodeficiency virus (HIV) viral proteins in terms selective regulation nuclear factor‐κB (NF‐κB) signaling without any effect on TBK1/IRF3 IFN production. The potential beneficial this cGAS–STING‐mediated, NF‐κB‐dependent effect, possible detrimental pathogenesis disease 2019 HIV infection deserve more attention future investigation.

Language: Английский

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Plasmacytoid Dendritic Cells, the Expression of the Stimulator of Interferon Genes Protein (STING) and a Possible Role of Th17 Immune Response in Cervical Lesions Mediated by Human Papillomavirus

Indian Journal of Microbiology, Journal Year: 2023, Volume and Issue: 63(4), P. 588 - 595

Published: Nov. 9, 2023

Language: Английский

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Endogenous Retroviruses Unveiled: A Comprehensive Review of Inflammatory Signaling/Senescence-Related Pathways and Therapeutic Strategies

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Endogenous retroviruses (ERVs), a subset of genomic transposable elements (TEs) in broader sense, have remained latent within mammalian genomes for tens millions years. These genetic are typically silenced state due to stringent regulatory mechanisms. However, under specific conditions, they can become activated, triggering inflammatory responses through diverse This activation has been shown play potential role various neurological disorders, tumors, and cellular senescence. Consequently, the regulation ERV expression methods holds promise clinical applications disease treatment. ERVs also engage interactions with variety exogenous viruses, thereby influencing outcomes viral infectious diseases. article comprehensively reviews pathogenic cascade ERVs, encompassing activation, inflammation, associated diseases, senescence, interplay viruses. Additionally, it outlines therapeutic strategies targeting aim offering novel research directions understanding relationship between along corresponding treatment modalities.

Language: Английский

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Interferons in human papillomavirus infection: antiviral effectors or immunopathogenic role?

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 193 - 216

Published: Nov. 1, 2024

Language: Английский

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