Sestrin2 remedies neuroinflammatory response by inhibiting A1 astrocyte conversion via autophagy DOI

Zhenguo Pan,

Xiaoyu Yu, Weiwei Wang

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: May 17, 2024

Abstract Most central nervous diseases are accompanied by astrocyte activation. Autophagy, an important pathway for cells to protect themselves and maintain homeostasis, is widely involved in regulation of Reactive astrocytes may play a protective or harmful role different due phenotypes astrocytes. It urgent task clarify the formation mechanisms inflammatory phenotype, A1 Sestrin2 highly conserved protein that can be induced under variety stress conditions as potential oxidative damage process. However, whether affect autophagy involve conversion still uncovered. In this study, we reported were significantly mouse hippocampus after multiple intraperitoneal injections lipopolysaccharide, with elevation mediators. Knockdown C8‐D1A promoted levels marker C3 mRNA factors, which was rescued inducer rapamycin. Overexpression attenuated reduced factor via abundant autophagy. Moreover, overexpression improved mitochondrial structure morphology. These results suggest suppress neuroinflammation inhibiting autophagy, drug target treating neuroinflammation. image

Language: Английский

cGAS–STING, an important signaling pathway in diseases and their therapy DOI Creative Commons
Qijie Li,

Ping Wu,

Qiujing Du

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: March 23, 2024

Abstract Since cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism cGAS–STING past decade. Meanwhile, triggering transduction mechanisms have continuously illuminated. plays a key role human diseases, particularly DNA‐triggered inflammatory making it potentially effective therapeutic target for inflammation‐related diseases. Here, we aim summarize ancient origin defense mechanism, as well triggers, transduction, cGAS–STING. We will also focus on important roles signal under pathological conditions, such infections, cancers, autoimmune neurological visceral inflammations, review drug development targeting pathway. The main directions potential obstacles research diseases cancers be discussed. These advancements expand our understanding cGAS–STING, provide theoretical basis further exploration open up new strategies promising intervention multiple

Language: Английский

Citations

23
Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Language: Английский

Citations

3
Influence of the brain‑gut axis on neuroinflammation in cerebral ischemia‑reperfusion injury (Review) DOI Creative Commons

Yifeng Zhang,

Hang Yang,

Shuai Hou

et al.

International Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 53(3)

Published: Jan. 29, 2024

Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut‑brain‑microbiota axis (GBMA) cerebral ischemia‑reperfusion has increasingly become focal point of scientific exploration, emerging as pivotal research avenue in stroke pathophysiology. In present review, authors delved into nexus GBMA neuroinflammation observed post‑stroke. analysis underscored roles histone deacetylase 3 neutrophil extracellular traps subsequent incidents. influence gut microbial compositions their metabolites, notably short‑chain fatty acids trimethylamine N‑oxide, on neuroinflammatory processes, was further elucidated. involvement immune cells, especially regulatory T‑cells, signaling cascades including cyclic GMP‑AMP synthase/stimulator interferon genes/Toll‑like receptor, emphasized complex mechanisms ischemia/reperfusion injury (CI/RI). Collectively, review offered comprehensive perspective metabolic, inflammatory modulations orchestrated by GBMA, augmenting understanding its role following CI/RI.

Language: Английский

Citations

3
Chasing Virus Replication and Infection: PAMP-PRR Interaction Drives Type I Interferon Production, Which in Turn Activates ISG Expression and ISGylation DOI Creative Commons
Iftikhar Muhammad,

Kaia M. Contes,

Moses T. Bility

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 528 - 528

Published: April 4, 2025

The innate immune response, particularly the interferon-mediated pathway, serves as first line of defense against viral infections. During virus infection, pathogen-associated molecular patterns (PAMPs) are recognized by host pattern recognition receptors (PRRs), triggering downstream signaling pathways. This leads to activation transcription factors like IRF3, IRF7, and NF-κB, which translocate nucleus induce production type I interferons (IFN-α IFN-β). Once secreted, bind their (IFNARs) on surfaces infected neighboring cells, activating JAK-STAT pathway. results in formation ISGF3 complex (composed STAT1, STAT2, IRF9), translocates drives expression interferon-stimulated genes (ISGs). Some ISGs exert antiviral effects directly or indirectly blocking infection replication. Among these ISGs, ISG15 plays a crucial role ISGylation process, ubiquitin-like modification that tags proteins, regulating responses inhibiting However, viruses have evolved counteractive strategies evade ISG15-mediated immunity ISGylation. review outlines PAMP-PRR-induced pathways leading cytokines followed summary ISGylation’s evasion mechanisms targeting ISGYlation.

Language: Английский

Citations

0
Sestrin2 remedies neuroinflammatory response by inhibiting A1 astrocyte conversion via autophagy DOI

Zhenguo Pan,

Xiaoyu Yu, Weiwei Wang

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: May 17, 2024

Abstract Most central nervous diseases are accompanied by astrocyte activation. Autophagy, an important pathway for cells to protect themselves and maintain homeostasis, is widely involved in regulation of Reactive astrocytes may play a protective or harmful role different due phenotypes astrocytes. It urgent task clarify the formation mechanisms inflammatory phenotype, A1 Sestrin2 highly conserved protein that can be induced under variety stress conditions as potential oxidative damage process. However, whether affect autophagy involve conversion still uncovered. In this study, we reported were significantly mouse hippocampus after multiple intraperitoneal injections lipopolysaccharide, with elevation mediators. Knockdown C8‐D1A promoted levels marker C3 mRNA factors, which was rescued inducer rapamycin. Overexpression attenuated reduced factor via abundant autophagy. Moreover, overexpression improved mitochondrial structure morphology. These results suggest suppress neuroinflammation inhibiting autophagy, drug target treating neuroinflammation. image

Language: Английский

Citations

2