Advances in neurotoxicology, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)
Опубликована: Фев. 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.
Язык: Английский
Процитировано
3
Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)
Опубликована: Март 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.
Язык: Английский
Процитировано
1
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(6), С. 189183 - 189183
Опубликована: Сен. 19, 2024
Язык: Английский
Процитировано
4
Neurosurgical Review, Год журнала: 2025, Номер 48(1)
Опубликована: Янв. 23, 2025
Язык: Английский
Процитировано
0
Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160667 - 160667
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Molecular Biology Reports, Год журнала: 2025, Номер 52(1)
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Cellular and Molecular Neurobiology, Год журнала: 2025, Номер 45(1)
Опубликована: Апрель 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
Язык: Английский
Процитировано
0
Neurobiology of Disease, Год журнала: 2024, Номер 202, С. 106710 - 106710
Опубликована: Окт. 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.
Язык: Английский
Процитировано
3
Aging Cell, Год журнала: 2024, Номер unknown
Опубликована: Окт. 16, 2024
Abstract Postoperative neurocognitive disorders (pNCD) are a common neurological complication, especially in elderly following anesthesia and surgery. Yet, the underlying mechanisms of pNCD remain elusive. This study aimed to investigate molecular that compromise synaptic metaplasticity development with focus on involvement Nogo‐66 receptor 1 (NgR1) pathogenesis aged mice. Aged mice subjected laparotomy surgery exhibited anxiety‐like behavior contextual fear memory impairment. Moreover, procedure significantly increased NogoA NgR1 expressions, particularly hippocampal CA1 CA3 regions. increase led depolymerization F‐actin, attributed activation RhoA‐GTPase, resulting reduction dendritic spines changes their morphology. Additionally, these hindered efficient postsynaptic delivery subunit GluA1 GluA2 AMPA receptors (AMPARs), consequently diminishing excitatory neurotransmission hippocampus. Importantly, administering competitive antagonist peptide NEP1‐40 (Nogo‐A extracellular residues 1–40 amino acids Nogo‐66) Fasudil (a Rho‐kinase inhibitor) effectively mitigated impairments reversed deficits Our work indicates high Nogo66‐NgR1 signaling disrupts surface due F‐actin pathophysiology pNCD.
Язык: Английский
Процитировано
1
Viruses, Год журнала: 2024, Номер 16(9), С. 1373 - 1373
Опубликована: Авг. 29, 2024
The porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the Arteriviridae family is a single-stranded, positively stranded RNA virus. currently available PRRSV vaccines are mainly inactivated attenuated vaccines, yet none of commercial can provide comprehensive, long-lasting, effective protection against PRRSV. SR717 pyridazine-3-carboxamide compound, which commonly used as non-nucleoside STING agonist with antitumor antiviral activities. Nevertheless, there no evidence that has any effects In this study, dose-dependent inhibitory effect was observed numerous strains using qRT-PCR, IFA, WB methods. Furthermore, found stimulate production anti-viral molecules trigger activation signaling cascade known stimulator interferon genes (STING) pathway, contributed hindering reproduction viruses by certain margin. Collectively, these results indicate capable inhibiting infection in vitro may have potential an drug
Язык: Английский
Процитировано
0