Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 30, 2024

The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R's structure, activation, physiological roles, focusing on its expression function microglial cells. article examines receptor's involvement calcium signaling, polarization, well role pathogenesis Alzheimer's disease, Parkinson's multiple sclerosis, amyotrophic lateral sclerosis. highlights complex nature P2X7R discussing potential neuroprotective neurotoxic effects depending disease stage context. It also addresses development antagonists their progress clinical trials, identifying key research gaps future perspectives P2X7R-targeted therapy development. By providing comprehensive overview state knowledge directions, this serves valuable resource researchers clinicians interested exploring targeting treatment

Language: Английский

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The role of gastrodin in the management of CNS‐related diseases: Underlying mechanisms to therapeutic perspectives

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(11), P. 5107 - 5133

Published: Aug. 15, 2024

Abstract Central nervous system (CNS)‐related diseases have a high mortality rate, are serious threat to physical and mental health, always been an important area of research. Gastrodin, the main active metabolite Gastrodia elata Blume, used in Chinese medicine food, has wide range pharmacological effects, mostly related CNS disorders. This review aims systematically summarize discuss effects underlying mechanisms gastrodin treatment diseases, assess its potential for further development as lead drug both biomedicine traditional medicine. Studies on indicate that it may exert anti‐neurodegenerative, cerebrovascular protective, ameliorative diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression anxiety, sleep disorders through various mechanisms. To date, 110 products approved clinical use, but multicenter case–control studies relatively scarce. Preclinical confirmed can be treat CNS‐related However, concerns need addressed context likely non‐specific, assay interfering when is studied using vitro silico approaches, calling systematic assessment evidence date. High‐quality trials should priority evaluate therapeutic safety efficacy gastrodin. Further experimental research appropriate vivo models also needed, focusing neurodegenerative cerebral ischemic hypoxic brain damage caused by methamphetamine or heavy metals, epilepsy.

Language: Английский

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Bibliometric Analysis of Neuroinflammation and Postoperative Cognitive Dysfunction

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

ABSTRACT Background The occurrence and development of postoperative cognitive dysfunction (POCD) are closely linked to neuroinflammation. This bibliometric analysis aims provide novel insights into the research trajectory, key topics, potential future trends in field neuroinflammation‐induced POCD. Methods Web Science Core Collection (WoSCC) database was searched identify publications from 2012 2023 on Bibliometric analysis, involving both statistical visual analyses, conducted using CiteSpace, VOSviewer, R software. Results Research POCD has exhibited an increasing trend over past 12 years. China had highest number publications, Nanjing Medical University most collaboration with other institutions, Zhiyi Zuo published author, Journal Neuroinflammation served as primary publication frequent keyword Keyword clustering indicated that predominant cluster is dexmedetomidine. Burst detection revealed delirium (POD), perioperative neurocognitive disorders (PND), apoptosis, epigenetic modifications were trends. Conclusions Our identified following areas associated POCD: anesthesia, surgery, dexmedetomidine, NLRP3 inflammasome, mechanism topics comprise POD, PND, modifications.

Language: Английский

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CCL17/CCR4 Axis Promotes Hematoma Clearance via ERK/AP1/SRA‐Mediated Microglial Polarization After Intracerebral Hemorrhage

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

Our previous studies demonstrated that CCL17 and its receptor CCR4 play crucial roles in neuroinflammation microglial activation following intracerebral hemorrhage (ICH). However, the specific mechanisms by which CCL17/CCR4 axis regulates polarization hematoma clearance remain unclear. This study investigates how signaling pathway modulates phenotype transition enhances resolution after ICH, building upon our earlier findings showing CCR4's involvement neuroinflammatory responses. Using CRISPR-mediated disruption overexpression approaches a mouse ICH model, we examined neurological outcomes, inflammatory responses, volumes. We further evaluated therapeutic potential of recombinant administration. The downstream ERK pathway's role CCL17/CCR4-mediated function was investigated through pharmacological inhibition. knockout exacerbated deficits, increased neuroinflammation, enlarged hematomas. In contrast, enhancing expression or administering improved functional recovery provided neuroprotection. Mechanistically, activated ERK/AP1/SRA pathway, promoting anti-inflammatory, phagocytic polarization, evidenced CD206 SRA expression. inhibition reversed these protective effects. extend work revealing pathway-mediated polarization. mechanism represents promising target for treatment.

Language: Английский

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Exploring the Nexus: How Ferroptosis, Microglia, and Neuroinflammation Converge in Ischemic Stroke Pathogenesis

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

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Targeting Neuroinflammation in Preterm White Matter Injury: Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: March 12, 2025

Neuroinflammation is a key factor in the development of preterm white matter injury (PWMI), leading to glial cell dysfunction, arrest oligodendrocyte maturation, and long-term neurological damage. As potential therapeutic strategy, mesenchymal stem cells (MSCs) exhibit significant immunomodulatory regenerative potential. Recent studies suggest that primary mechanism MSC action their paracrine effects, particularly mediated by extracellular vesicles, with MSC-derived exosomes (MSC-Exos) being mediators. MSC-Exos, enriched lipids, proteins, nucleic acids, regulate neuroinflammation modulating activity influencing signaling pathways associated inflammation repair. Preclinical evidence has indicated MSC-Exos can suppress activation microglia astrocytes, promote enhance myelination, highlighting as cell-free treatment for PWMI. However, there are paucity comprehensive reviews on how PWMI through specific pathways. This review aims summarize which modulate discuss challenges clinical application MSC-Exos-based therapies.

Language: Английский

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Kanglexin attenuates spinal cord injury by modulating pyroptosis and polarization via the PKA/NF-κB signaling pathway

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114401 - 114401

Published: March 17, 2025

Language: Английский

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Cannabinoid Receptor-2 Alleviates Sepsis-Induced Neuroinflammation by Modulating Microglia M1/M2 Subset Polarization Through Inhibiting Nogo-B Expression

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

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Enhanced inhibition of neuronal ferroptosis and regulation of microglial polarization with multifunctional traditional Chinese medicine active ingredient-based selenium nanoparticles for treating spinal cord injury

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101758 - 101758

Published: April 1, 2025

Language: Английский

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Activation of GPER1 alleviates white matter injury by promoting microglia M2 polarization through EGFR/Stat3 pathway in intracerebral hemorrhage mice

Journal of Stroke and Cerebrovascular Diseases, Journal Year: 2025, Volume and Issue: 34(6), P. 108315 - 108315

Published: April 12, 2025

White matter injury (WMI) is a major pathophysiological process after intracerebral hemorrhage (ICH). G protein-coupled estrogen receptor 1 (GPER1) has been validated to exert crucial role in regulating neuroinflammation and microglia polarization. Our previous report reveals activation of GPER1 improves the neurological deficits ICH via inhibition A1 astrocytes. However, on protection WMI modulation polarization remains unclear. In present study, mice model was induced by autologous whole blood injection vitro established treatment BV2 cells with FeSO4. Mice were treated agonist G1, antagonist G15 or EGFR inhibitor AG1478. Besides, conditional medium used intervene MO3.13 oligodendrocytes. Immunostaining, immunoblots, transmission electron microscope PI staining determine WMI, potential molecular mechanism ICH, respectively. data showed G1 ameliorated day 3 ICH. reduced release IL-1β, TNF-α increased produce IL-4, IL-10 as well shifting from proinflammatory M1 anti-inflammatory M2 phenotype vivo vitro. Meanwhile, alleviated oligodendrocytes death mitigating modulating Mechanistic study demonstrated EGFR/Stat3 signaling pathway involved Collectively, our findings through pathway.

Language: Английский

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