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

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
The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer’s disease DOI Creative Commons

Shuiyue Quan,

Xiaofeng Fu,

Huimin Cai

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 4, 2025

The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizing damage-associated molecular patterns (DAMPs), inducing the innate immune response by activating stimulator of interferon genes (STING). Dysregulation this pathway culminates in AD-related neuroinflammation neurodegeneration. A substantial body mitochondria are involved critical pathogenic mechanisms AD, whose damage leads release mitochondrial (mtDNA) into extramitochondrial space. This leaked mtDNA serves DAMP, various pattern recognition receptors defense networks brain, including cGAS-STING pathway, ultimately leading an imbalance homeostasis. Therefore, modulation mtDNA-cGAS-STING restore neuroimmune homeostasis may offer promising prospects for improving AD treatment outcomes. In review, we focus on during stress activation pathway. Additionally, delve research progress further discuss primary directions potential hurdles developing targeted therapeutic drugs, gain deeper understanding pathogenesis provide new approaches its therapy.

Language: Английский

Citations

1
Novel Insights into Neuroinflammatory Mechanisms in Traumatic Brain Injury: Focus on Pattern Recognition Receptors as Therapeutic Targets DOI

Harapriya Baral,

Ravinder K. Kaundal

Cytokine & Growth Factor Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges DOI Creative Commons

Beilei Yue,

Wenbo Gao, Jonathan F. Lovell

et al.

Essays in Biochemistry, Journal Year: 2025, Volume and Issue: 69(02)

Published: March 7, 2025

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a crucial component the host's innate immunity and plays central role in detecting cytosolic double-stranded DNA from endogenous exogenous sources. Upon activation, cGAS synthesizes cGAMP, which binds to STING, triggering cascade immune responses, including production type I interferons pro-inflammatory cytokines. In context cancers, cGAS-STING can exert dual roles: on one hand, it promotes anti-tumor by enhancing antigen presentation, stimulating T-cell inducing direct tumor cell apoptosis. On other chronic particularly tumors with chromosomal instability, lead suppression progression. Persistent signaling results up-regulation checkpoint molecules such as PD-L1, contributing evasion metastasis. Consequently, strategies targeting have consider balance activation tolerance caused activation. This review explores mechanisms underlying both protumor roles pathway, focus potential therapeutic approaches, challenges faced their clinical application, along corresponding solutions.

Language: Английский

Citations

0
Decoding Ischemic Stroke: Perspectives on the Endoplasmic Reticulum, Mitochondria, and Their Crosstalk DOI Creative Commons
Chuxin Zhang, Xin Lan, Qingguo Wang

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103622 - 103622

Published: March 1, 2025

Stroke is known for its high disability and mortality rates. Ischemic stroke (IS), the most prevalent form, imposes a considerable burden on affected individuals. Nevertheless, existing treatment modalities are hindered by limitations, including narrow therapeutic windows, substantial adverse effects, suboptimal neurological recovery. Clarifying pathological mechanism of IS prerequisite developing new strategies. In this context, functional disruption mitochondria, endoplasmic reticulum (ER), crosstalk mechanisms between them have garnered increasing attention their contributory roles in progression IS. Therefore, review provides comprehensive summary current pathomechanisms associated with involvement ER mitochondria IS, emphasising Ca2+ destabilization homeostasis, stress, oxidative disordered mitochondrial quality control, transfer. Additionally, article highlights interaction as well mitochondrial-ER contacts (MERCs) that structurally connect ER, aiming to provide ideas references research

Language: Английский

Citations

0
Unraveling the cGAS-STING pathway in Alzheimer’s disease: A new Frontier in neuroinflammation and therapeutic strategies DOI
Arshdeep Kaur, Khadga Raj Aran

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
The STING Signaling: A Novel Target for Central Nervous System Diseases DOI Creative Commons
Min Song,

Jianxun Ren,

Zhipeng Zhu

et al.

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

Citations

0
Molecular mechanism of PANoptosis and programmed cell death in neurological diseases DOI Creative Commons

Ketian Hou,

Weihong Pan,

L.-Y. Liu

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106907 - 106907

Published: April 1, 2025

PANoptosis represents a highly coordinated inflammatory programmed cell death governed by the assembly and activation of PANoptosome, which strategically integrate core molecular elements from pyroptosis, apoptosis, necroptosis. The triple-component pathways set themselves apart alternative regulated mechanisms through their unique capacity to concurrently process signals derived multiple death-signaling modalities, thereby coordinating multifaceted cellular defense system against diverse pathological insults. Pathogen-associated patterns synergistically interact with cytokine storms, oncogenic stress active PANoptosis, establishing this pathway as critical nexus in pathogenesis tumor immunomodulation. This crosstalk highlights promising therapeutic target for managing immune-related disorders malignant transformation. Emerging evidence links neuroinflammatory dysregulated between (apoptosis, necroptosis, pyroptosis) accidental necrosis, driving neuronal loss neural damage. Single-cell transcriptomics reveals spatially resolved signatures Alzheimer's hippocampal microenvironments sclerosis demyelinating plaques, distinct clusters correlating quantifiable metrics. PANoptosis-targeted therapies show preclinical promise alleviating neurovascular dysfunction while preserving physiological microglial surveillance functions. Accumulating linking (particularly PANoptosis) neurological underscores urgency deciphering its developing precision modulators next-generation therapies. review systematically deciphers PANoptosome associated cascades, evaluates roles multiscale regulatory networks, proposes frameworks advance neurology.

Language: Английский

Citations

0
Gelsevirine ameliorates sepsis-associated encephalopathy by inhibiting the STING signalling-mediated pyroptosis pathway in microglia DOI

Qingquan Zeng,

Jing Wang, Rongcai Yue

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 135, P. 156071 - 156071

Published: Sept. 19, 2024

Language: Английский

Citations

3
The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases DOI Creative Commons
Yuxin Zhang, Meijuan Zou, Hao Wu

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 202, P. 106710 - 106710

Published: Oct. 28, 2024

Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by damage to specific cell populations in the nervous system, ultimately leading disability or death. Effective treatments for these still lacking, due limited understanding their pathogeneses, which involve multiple cellular and molecular pathways. The triggering an immune response is feature neurodegenerative disorders. A critical challenge intricate interplay between neuroinflammation, neurodegeneration, responses, not yet fully characterized. In recent years, cyclic GMP-AMP synthase (cGAS)-stimulator interferon gene (STING) pathway, crucial intracellular DNA sensing, has gradually gained attention. However, roles this pathway within types such as cells, glial neuronal its contribution ND pathogenesis, remain elucidated. review, we systematically explore how cGAS-STING signaling links various with related effector pathways under context NDs multifaceted therapeutic directions. We emphasize discovery condition-dependent heterogeneity integral diverse responses potential targets. Additionally, review pathogenic role activation Parkinson's disease, ataxia-telangiectasia, amyotrophic lateral sclerosis. focus on complex bidirectional Alzheimer's Huntington's sclerosis, revealing double-edged nature disease progression. objective elucidate pivotal pathogenesis catalyze new insights facilitating development novel strategies.

Language: Английский

Citations

3