Current Neuropharmacology最新文献

{"title":"A Bibliometric Analysis of Mitochondrial Dysfunction in Spinal Cord Injury: Research Landscape and Emerging Trends, 2000-2025.","authors":"Yinuo Zhang, Yuntian Ji, Yuxin Qin, Xunpei Xu, Biao Yang, Zheng Zhang, Jiaojiao Feng, Rui Gao, Xuhui Zhou","doi":"10.2174/011570159X459060260820064854","DOIUrl":"https://doi.org/10.2174/011570159X459060260820064854","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal cord injury (SCI) is a severe central nervous system injury. Mitochondrial dysfunction is a key driver of the secondary injury cascade, disrupting energy metabolism and calcium homeostasis and activating cell death pathways. Although bibliometric approaches have been widely used to map research trends, hotspots, and knowledge structures across biomedical fields, systematic analyses of research at the intersection of SCI and mitochondrial dysfunction remain limited.</p><p><strong>Methods: </strong>Relevant publications on mitochondrial dysfunction in SCI published between 2000 and 2025 were retrieved from the Web of Science Core Collection (WoSCC). After screening according to predefined eligibility criteria, 993 articles and reviews were included. Bibliometrix, VOSviewer, and CiteSpace were used for bibliometric analysis and visualization of publication output, countries and institutions, authors, journals, co-citation networks, and keywords.</p><p><strong>Results: </strong>Annual publication output increased exponentially (R² = 0.9453), with particularly rapid growth after 2017. China produced the most publications (n = 442), whereas the United States received the most total citations (25,855). The University of Kentucky ranked first in institutional publication output, while several Chinese institutions showed strong recent citation bursts. Patrick G. Sullivan was a prominent early contributor, whereas Xifan Mei exhibited the strongest recent author burst. Keyword analysis identified five major thematic clusters and indicated a temporal shift in research emphasis from apoptosis-related mechanisms toward inflammation, regeneration, and immunometabolism.</p><p><strong>Discussion: </strong>The number of publications in this field has grown rapidly since 2017, reflecting increasing research attention to mitochondrial dysfunction and mitochondria-targeted therapeutic strategies. Keywords indicate that the research topic has gradually expanded from mechanism research focused on apoptosis to inflammation, regeneration, and immunometabolism. Mitochondria may be an important regulator of the inflammation and regeneration microenvironment after SCI. Given the complexity of the secondary injury cascade, a single-target intervention strategy makes it difficult to achieve optimal recovery of neurological function.</p><p><strong>Conclusion: </strong>This first bibliometric study, focusing on spinal cord injury and mitochondria, demonstrates that the field is advancing rapidly and exhibits distinct translational research orientations. Immunemetabolism has emerged as a novel research frontier, yet relevant clinical trials in this area remain scarce, underscoring the need to accelerate the translation of basic research outcomes into clinical practice.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of the Vascular and Neuronal Role of L-Carnosine: Mechanistic and Pharmacological Perspectives.","authors":"Nidhi Tiwari, Vivek Kumar, Bhuwan Chandra Joshi, Abdulaziz S Saeedan, Summya Rashid, Mohd Nazam Ansari","doi":"10.2174/011570159X462604260803095102","DOIUrl":"https://doi.org/10.2174/011570159X462604260803095102","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;L-carnosine is a powerful natural antioxidant found in the brain, muscles, and digestive systems of all vertebrates, including humans, that helps fight Reactive Oxygen Species (ROS) and other harmful byproducts of oxidative stress. L-carnosine has antioxidant properties as well as the ability to bind with metal ions and prevent glycation, a process that can damage cells. This review article highlights the protective effects of L-carnosine against a variety of pathological conditions, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), ischemia‒reperfusion injury, Huntington's disease, stroke, depression, traumatic brain injury, cancer, diabetes, ageing, etc. Among these conditions, mitochondrial dysfunction and increased oxidative stress are common. Moreover, methylglyoxal (MG), another metabolic product, and Advanced Glycation End products (AGEs) damage cells through interactions with proteins. Through receptor-mediated endocytosis, macrophages absorb them and release proinflammatory chemicals that induce severe inflammation and lead to cell death.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Search engines, including PubMed, ScienceDirect, ProQuest, Scopus, ResearchGate, MDPI, journals, websites, and databases such as Google Scholar, were thoroughly searched and reviewed. The search strategy for articles published between 2000 and 2025 used various combinations of key Medical Subject Headings (MeSH) terms and phrases, including L-carnosine, alanine, histidine, Randomized Controlled Trial (RCT), aging, cancer, cardiovascular disease, diabetes, and neurodegenerative disorders, and various non-MeSH terms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;L-carnosine exhibits protective effects on models of neurological, ischemic, metabolic, and malignant diseases because of its antioxidant, anti-inflammatory, and neuroprotective properties. In Alzheimer's disease, carnosine specifically increases the production of heat shock proteins (Hsps). In Parkinson's disease, it increases dopamine levels and stops alpha-synuclein protein accumulation. In ischemia‒reperfusion injury, L-carnosine inhibits the release of inflammatory mediators such as cytokines and TNF-alpha. In cancer, it inhibits the Mitogen-Activated Protein Kinase (MAPK)/ Extracellular Signal-Related Kinase (ERK) signaling pathway. It mitigates aging-related damage to proteins. Additionally, L-carnosine inhibits the formation of MG and AGEs, suggesting its potential therapeutic efficacy in a range of diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;L-carnosine shows multitarget therapeutic potential through antioxidant, anti-inflammatory, and antiglycation actions, as well as mitochondrial protection. It influences key pathways involved in neurodegeneration, including protein aggregation and oxidative stress. Evidence from preclinical and early clinical studies suggests benefits in neurological and metabolic disorders. Despite promising outcomes, challenges such as rapid degradation ","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect and Potential Pharmacological Mechanism of Tauroursodeoxycholic Acid for Spinal Cord Injury: A Systematic Review and Network Pharmacology.","authors":"Yi-Xuan Wang, Jia-Xuan Zhang, Meng-Jie Zhang, Yu Xiao, Zhuo-Yao Li, Bi-Meng Zhang, Yong-Jun Wang, Xue-Jun Cui, Ai-Fang Zhou, Min Yao","doi":"10.2174/011570159X441882260803055824","DOIUrl":"https://doi.org/10.2174/011570159X441882260803055824","url":null,"abstract":"<p><strong>Background: </strong>Spinal Cord Injury (SCI) is a highly disabling disease owing to unexpected mechanical damage, which may trigger serious complications. Tauroursodeoxycholic Acid (TUDCA) serves as a neuroprotective agent for SCI. Therefore, this study assessed the effect of TUDCA for intervening in SCI in existing preclinical tests, with a summary of its mechanism simultaneously.</p><p><strong>Methods: </strong>This systematic review was presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Literature retrieval, without language restriction, to identify in vivo studies on SCI treatment using TUDCA was performed by searching databases such as PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and SinoMed from their inception to May 2025, coupled with the collection of grey literature. Literature retrieval and risk-of-bias assessment using SYRCLE's RoB tool were independently conducted by two reviewers. A subsequent meta-analysis was conducted using the Review Manager 5.4 software. In addition, network pharmacology combined with molecular docking was utilized to explore the potential mechanism of TUDCA in treating SCI.</p><p><strong>Results: </strong>A total of 14 studies were finally enrolled, over half of which had at least 5 items rating low risk of bias. The results of the meta-analysis showed that motor function, as assessed by the BBB score, was significantly enhanced after TUDCA treatment (14th day; WMD = 3.11 [1.84 to 4.37], p < 0.0001). Meanwhile, the inclined plane test and TUNEL indicated that TUDCA contribut-ed to SCI recovery. Subgroup analysis suggested a more pronounced effect of TUDCA in females (WMD = 3.76 [2.51, 5.10], p < 0.0001) than in males. Moreover, TUDCA at 200 mg/kg improved motor function (WMD = 2.90 [2.03, 3.77]; p < 0.0001). Network pharmacology identified AKT1, EGFR, HSP90AA1, and SRC as key targets, with the identification of PI3K-Akt, Foxo, estrogen signaling pathway, and apoptosis, etc. Molecular docking suggested that PPARγ, PARP1, and GSK3β bound to TUDCA better. Additionally, this review revealed the unique advantages and potential mechanisms of TUDCA, supporting the potential of neuroprotective agents for SCI treatment.</p><p><strong>Discussion: </strong>The identified optimal dose and sex-dependent efficacy of TUDCA provide critical insights for its future development as a neuroprotective agent. Network pharmacology and molecular docking provide sufficient evidence for SCI treatment with TUDCA.</p><p><strong>Conclusion: </strong>TUDCA can enhance neuronal autophagy and inhibit inflammatory factor expression, reducing inflammatory response and suppressing neuronal apoptosis in SCI. Due to the limited number and uneven quality of included studies, further laboratory studies and validation in clinical trials are necessary to clarify the neuroprotective effect of TUDCA.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-Derived Exosomes in Neurodegenerative Disorders and Age-Related Brain Dysfunction: From Isolation to Clinical Potential.","authors":"Damla Aykora, Metehan Uzun","doi":"10.2174/011570159X456941260803062544","DOIUrl":"https://doi.org/10.2174/011570159X456941260803062544","url":null,"abstract":"<p><strong>Introduction: </strong>Plant-derived Exosome-like Nanovesicles (PELNs) have the potential to exhibit improved biological functions in multiple pathological disorders, particularly in neurodegenerative and age-related brain diseases. In this review, advanced isolation techniques, including Differential Ultracentrifugation (dUC), Size-Exclusion Chromatography (SEC), and Polyethylene Glycol (PEG) precipitation, were systematically evaluated to optimize the structural integrity, purity, and biological activity of PELNs.</p><p><strong>Methods: </strong>Novel studies on PELNs were the primary focus of this review. Evidence-based studies were compared and discussed in terms of chemical and functional characteristics, as well as optimized production strategies to enhance the therapeutic properties of PELNs.</p><p><strong>Results: </strong>According to the consensus of reviewed studies, PELNs demonstrate efficient cellular uptake due to their lipophilic chemical structures and modulate intracellular signaling pathways related to neurodegeneration. The main drawbacks of PELNs' utilization mostly depend on the extraction methods and limited delivery through the BBB. A combination of optimized methods, such as dUC and SEC, may exhibit maintained therapeutic strategies for neurological applications.</p><p><strong>Discussion: </strong>Due to the limited number of experimental studies in Parkinson's Disease (PD) and Alzheimer's Disease (AD), and brain aging, advances in PELNs extraction methods have been shown to enhance BBB delivery and therapeutic efficacy. Every study claims the superiority of its own method; however, none of these methods fully addresses the limitations inherent in producing optimal results.</p><p><strong>Conclusion: </strong>PELNs represent a promising platform for neurological dysfunction and brain aging-related disorders. However, isolation and characterization methods must be carefully optimized and validated to ensure the production of therapeutically active PELNs suitable for BBB delivery.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Management of Diabetic Neuropathy: Current Evidence, Clinical Positioning, and Emerging Therapeutic Targets.","authors":"Ali Hikmat Alburghaif, Hany Akeel Al-Hussaniy, Jihad Maan, Nargis Abdul Razzaq","doi":"10.2174/011570159X455049260809205038","DOIUrl":"https://doi.org/10.2174/011570159X455049260809205038","url":null,"abstract":"<p><strong>Background: </strong>Diabetic neuropathy is one of the most serious complications of diabetes mellitus, which is associated with pain, loss of sensation, and numbness in the extremities. Several cellular triggers, such as oxidative stress, inflammation, and glycation products, all cause nerve damage. These changes affect quality of life and may cause ulcers or amputations, so effective management is essential.</p><p><strong>Objectives: </strong>This review is conducted to identify and summarize the main pharmacological strategies that are used in the treatment of diabetic neuropathy, both the approved treatments and those that are currently under research.</p><p><strong>Methods: </strong>This review was conducted by searching scientific databases and repositories, including Google Scholar, PubMed, and DOAJ, using keywords such as diabetic neuropathy, pharmacological treatment of pain, and antidepressant. After excluding articles, the final number of articles included in our study was approximately 107, comprising clinical studies and review articles.</p><p><strong>Results: </strong>Tricyclic antidepressants as well as serotonin-norepinephrine reuptake inhibitors have been proven to help with neuropathic pain but can be associated with sedation or gastrointestinal side effects. The anticonvulsants, including pregabalin and gabapentin, decrease neuronal excitability and are reliable in reducing pain. Local therapies, such as capsaicin and lidocaine, are more local and less systemic. Opioids are also used in the treatment of recalcitrant cases due to risks of tolerance and dependence. Other recent alternatives, such as alpha-lipoic acid and erythropoietin, show promise for antioxidant and neuroprotective effects.</p><p><strong>Discussion: </strong>In addition to traditionally approved medications, several drugs were tested as promising treatments. One of them is suzetrigine (VX548), which reduces pain and is recognized as a potential none opioid option. Engensis (VM202) also has clinical benefits. Acetyl-L-carnitine and Cibinetide (ara290) also show improvement in the Neuropathic score; other treatments, such as Nicotinamide riboside, after long-term use, were associated with symptomatic relief of pain.</p><p><strong>Conclusion: </strong>Managing diabetic neuropathy necessitates personalized treatment that equilibrates analgesia with tolerability. Current medications primarily alleviate symptoms; however, ongoing investigations into antioxidant and neuroprotective agents present the potential for therapies that may decelerate or reverse nerve damage.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregabalin: A Multifunctional Modulator in Neuropathic Pain and Beyond.","authors":"Ali Mahmoud Al-Samydai, Kadhim Adnan Ali, Ali Hikmat Alburghaif, Hany Akeel Al-Hussaniy","doi":"10.2174/011570159X474079260809185654","DOIUrl":"https://doi.org/10.2174/011570159X474079260809185654","url":null,"abstract":"<p><strong>Introduction: </strong>Pregabalin is a structural analogue of γ-aminobutyric acid (GABA) that functions as a potent modulator of excitatory neurotransmission through high-affinity binding to the α2δ subunit of voltage-gated calcium channels. This review provides a comprehensive overview of its pharmacological properties, clinical efficacy, and therapeutic scope across neuropathic and non-neuropathic conditions.</p><p><strong>Method: </strong>This review is a narrative, descriptive, and integrative type of review conducted using current evidence regarding pharmacology, therapeutic applications, comparative efficacy, and pregabalin safety profile.</p><p><strong>Results: </strong>Pregabalin exhibits rapid absorption, high bioavailability, linear pharmacokinetics, renal elimination, and minimal hepatic metabolism, supporting predictable dosing. Clinically, it demonstrates proven efficacy in neuropathic pain syndromes, including diabetic neuropathy, postherpetic neuralgia, fibromyalgia, and spinal cord injury-related pain, where it acts as a first-line or adjunctive agent. Beyond analgesia, pregabalin serves as an adjunct in partial seizures, a recognized treatment for generalized anxiety disorder, and an emerging option for sleep disturbances and comorbid psychiatric conditions. Comparative analyses indicate similar or superior efficacy to gabapentin and other first-line agents, with added benefit in improving sleep and global function. Adverse effects such as dizziness, somnolence, and peripheral edema are generally mild and dose-related.</p><p><strong>Discussion: </strong>Future studies should clarify its role in treatment-resistant pain, psychiatric comorbidities, and sleep-related disorders to optimize its clinical use.</p><p><strong>Conclusion: </strong>Owing to its favorable safety profile, limited drug-drug interactions, and broad therapeutic potential, pregabalin remains an essential component of neuropathic pain.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropharmacology in the Era of Precision Medicine: From Synaptic Targets to Personalized Therapies.","authors":"Laith Al-Eitan","doi":"10.2174/011570159X478420260805095437","DOIUrl":"https://doi.org/10.2174/011570159X478420260805095437","url":null,"abstract":"<p><p>Neuropsychiatric and neurodegenerative disorders show wide variability in treatment response, thus limiting the effectiveness of traditional symptom-based neuropharmacology. Precision medicine offers a more targeted approach by combining pharmacogenomics, multi-omics data, and artificial intelligence to guide individualized therapy. It's a rapidly evolving field with demonstrable promise, but its broader clinical integration still depends on stronger biomarker validation, reproducibility across populations, equitable implementation, regulatory maturity, and prospective clinical utility studies. Genetic markers could predict drug metabolism, while multi-omics profiling enables the identification of disease-specific molecular patterns; in parallel, AI tools improve treatment prediction, integrate complex datasets, and accelerate drug discovery. Although some of these approaches are already used in clinical practice, most remain under development. This review presents a multi-layered approach that includes neurotransmitter pathways, pharmacogenomics, multi-omics analysis, artificial intelligence, and translational science, providing a more holistic insight and bridging the gap between synaptic mechanisms and personalized treatments.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Serum NGF and BDNF Levels in People Living with HIV According to Antiretroviral Therapy, Historical and Current Viroimmunological Condition: A Pilot Study.","authors":"Luca Maddaloni, Pamela Rosso, Elena Fico, Letizia Santinelli, Carmen Falvino, Marco Ridolfi, Giampiero Ferraguti, Giancarlo Ceccarelli, Claudio Maria Mastroianni, Guido Antonelli, Carolina Scagnolari, Gabriella d'Ettorre, Marco Fiore","doi":"10.2174/011570159X476515260713105822","DOIUrl":"https://doi.org/10.2174/011570159X476515260713105822","url":null,"abstract":"<p><strong>Introduction: </strong>Although HIV infection can now be kept under control in almost all people living with HIV (PLWH), these individuals are prone to developing several non-AIDS complications due to chronic immune impairments, such as HIV-associated neurocognitive disorders (HAND). Unfortunately, no marker has been identified to predict these conditions, but there is growing interest in neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF).</p><p><strong>Methods: </strong>In this pilot study, we evaluated the serum levels of these neurotrophins in 13 antiretroviral therapy (ART)-naive and 12 ART-treated PLWH, and in two matched groups of 13 and 12 HIVnegative volunteers, respectively.</p><p><strong>Results: </strong>ART-naive PLWH showed higher levels of NGF (p = 0.0036) and lower levels of BDNF (p < 0.0001) in their serum compared to HIV-negative individuals. In contrast, the neurotrophin levels of ART-treated PLWH were similar to those of HIV-negative people. Furthermore, serum NGF showed a negative correlation with blood CD4+ T cell count and a positive correlation with peak (zenith) HIV-RNA. Conversely, serum BDNF had a positive correlation with blood CD4+ T cell count and CD4/CD8 ratio.</p><p><strong>Discussion: </strong>The dysregulation in neurotrophin homeostasis due to HIV infection appears to be restricted to ART-naive individuals. However, NGF and BDNF levels remain influenced by both the viro-immunological status at diagnosis and the current immune status, even after effective ART.</p><p><strong>Conclusion: </strong>These findings suggest a distinct neurotrophin signature in untreated HIV infection, as well as a strong correlation between NGF and BDNF levels and current or historical immune status. This supports the need for further exploration of neurotrophins as potential biomarkers of HAND.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting NMDA Receptor Pathways in Alzheimer's Disease, From Cellular Mechanisms to Treatment Strategies.","authors":"Md Sirajuddin Khan, Astik Manju Ashesh, Mithul V Mammen, Abdulrahman Alhusaini, Talha Jawaid, Md Sayeed Akhtar, Khalid Orayj, Israr Ansari, Dileep Kumar, Ajay Kumar","doi":"10.2174/011570159X474645260731070203","DOIUrl":"https://doi.org/10.2174/011570159X474645260731070203","url":null,"abstract":"<p><p>The Alzheimer's Disease (AD) lacks effective disease-modifying therapy, even though amyloid-targeting immunotherapies have recently been applied clinically. N-methyl-D-Aspartate Receptors (NMDARs) play a central yet mechanistically complicated role in the pathophysiology of AD, where they are convergence points of amyloid-beta (Aβ) oligomer toxicity, tau-dependent excitotoxicity, and progressive synaptic failure. This critical review examines NMDAR dysfunction across the AD spectrum, with a focus on subunit-regulated signalling, subcellular localisation, and subsequent pathological cascades. The effects of Aβ oligomers on NMDAR activity involve multiple mechanisms that disrupt their function, including glutamate dysregulation mediated by GLT-1, redistribution of GluN2B to extrasynaptic areas, and inhibition of JAK2-CREB via activation of extrasynaptic receptors. Tau enhances excitotoxic injury throughdendritic mislocalization, and the tau-Fyn-GluN2B complex, which propels pro-death signalling by DAPK1. This conceptually important prevailing synaptic-extrasynaptic dichotomy is fiercely criticised here, given evidence that synaptic receptors containing GluN2A also mediate pathological signalling during sustained Aß exposure, and that tri-heteromeric receptor populations are problematic for subunit-selective targeting. Neuroinflammation, dysfunction of the blood-brain barrier, and excitotoxic amplification via GluN2C/D-enriched receptor pools in neurons, astrocytes, microglia, oligodendrocytes, and endothelial cells are underexplored therapeutic targets for neurodegenerative disease (non-neuronal NMDARs). Memantine is the only approved NMDAR-targeting agent for AD. Subunit-selective antagonists have not been translated into clinical use, and the positive allosteric modulator dalzanemdor (SAGE-718) did not pass its randomised Phase 2 trial in 2024. The most mechanistically justified approach is to advance subunit-selective, compartment-specific, or protein-complexdisrupting strategies. Although it is not established whether any single NMDAR-targeting intervention will suffice as a disease-modifying therapy, the convergence of molecular, genetic, and clinical evidence positions NMDAR dysfunction as a tractable , if therapeutically demanding , node in the AD pathogenic network, warranting continued, mechanism-informed drug discovery.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7 Receptor Modulators from Natural Products: Their Actions on Inflammatory and Painful Chronic Diseases.","authors":"Raíssa Maria Dos Santos Galvão, Ana Luisa Palhares de Miranda, Robson Xavier Faria","doi":"10.2174/011570159X338338250318062435","DOIUrl":"10.2174/011570159X338338250318062435","url":null,"abstract":"<p><p>This study investigates the therapeutic potential of compounds derived from natural products as anti-inflammatory and analgesic agents. It focuses on their ability to modulate the P2X7 receptor, a key protein involved in purinergic signaling that plays a crucial role in the inflammatory response and pain transmission. The goal is to identify promising candidates for developing new treatments for chronic inflammation, neuropathic pain, and cancer, highlighting the relevance of natural sources for safer, sustainable therapies. These compounds could serve as prototypes for new anti-inflammatory and analgesic drugs, including P2X7 receptor antagonists. A search of databases, including PubMed and Google Scholar, was performed to identify relevant studies published since 2017. Search terms included \"P2X7 receptor\", \"natural products\", \"inflammatory diseases\" and \"neuropathic pain\". Additional articles were identified through manual searching of reference lists. The review identified 35 studies exploring the effects of natural products on purinergic signaling, targeting the P2X7 receptor. These studies highlighted 24 plant species and 36 compounds for their anti-inflammatory and analgesic properties, focusing on P2X7 receptor modulation. Significant findings included inhibition of inflammatory mediators and pain relief, measured by IC50 values. This review concludes that these natural products are promising for developing new anti-inflammatory agents, given their inhibition of inflammatory mediators and the P2X7 receptor. The diverse activities of these phytochemicals offer potential treatments for chronic diseases associated with inflammation and pain. Further research on mechanistic actions and clinical efficacy is necessary to validate their therapeutic potential and develop effective phytotherapeutics.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}