Current Neuropharmacology最新文献

{"title":"Celastrol Ameliorates Vincristine-induced Neuropathic Pain by Inhibiting Spinal Astrocyte Hyperactivation-mediated Inflammation, Oxidative Stress, and Apoptosis.","authors":"Gui-Zhou Li, Jing Xu, Yun-Man Li, Ya-Hui Hu","doi":"10.2174/011570159X385690250509050208","DOIUrl":"https://doi.org/10.2174/011570159X385690250509050208","url":null,"abstract":"<p><strong>Background: </strong>Neurotoxicity is the severe adverse reaction induced by chemotherapy drugs, characterized by neuropathic pain. However, there is a notable lack of therapeutic drugs for chemotherapy-induced neuropathic pain (CINP). Celastrol, a naturally occurring terpenoid active compound extracted from the roots of Tripterygium wilfordii Hook f., exhibits a neuroprotective effect, yet its therapeutic potential in CINP has not been reported.</p><p><strong>Objective: </strong>In this study, with vincristine-induced neuropathic pain (VINP) as a model, we aimed to investigate the therapeutic effect of celastrol on VINP and its specific mechanisms.</p><p><strong>Methods: </strong>Vincristine (VCR, 0.1 mg/kg, intraperitoneal injection) was used to induce a neuropathic pain model. Celastrol (0.5, 1.0, and 2.0 mg/kg, intraperitoneal injection) was administered to assess its therapeutic effects on vincristine-induced neuropathic pain (VINP). Transmission electron microscopy (TEM) was employed to examine damage to the sciatic nerve fibers and mitochondria. Flow cytometry was used to detect mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and cell apoptosis. Primary astrocyte cultures were utilized further to validate the therapeutic mechanisms of celastrol in VINP.</p><p><strong>Results: </strong>Here, we demonstrate that celastrol inhibits vincristine (VCR)-induced activation of spinal astrocytes by suppressing CaMKII phosphorylation. Additionally, celastrol alleviates the Cx43- dependent inflammation caused by VCR through the inhibition of the CaMKII/NF-κB signaling pathway. Concurrently, celastrol modulates the production of reactive oxygen species (ROS) and the expression of apoptosis-related proteins (Cleaved Caspase-3, Bax, and Bcl-2) by suppressing the phosphorylation of CaMKII in astrocytes, thereby ameliorating the mitochondrial damage and cell apoptosis caused by VCR.</p><p><strong>Conclusion: </strong>Our findings reveal that celastrol exerts therapeutic effects on VINP through its antiinflammatory, antioxidant, and anti-apoptotic properties. Furthermore, we preliminarily explore the molecular mechanisms underlying these effects, thereby providing a scientific basis for celastrol as a potential therapeutic agent for CINP.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076450","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":"Translational Informatics for Neuropharmacology: Databases, Ontologies, and Analytics.","authors":"Bairong Shen, Nigel H Greig, Mohammad Amjad Kamal","doi":"10.2174/011570159X411123250509100901","DOIUrl":"https://doi.org/10.2174/011570159X411123250509100901","url":null,"abstract":"","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076456","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 Evolution of Machine Learning in Medicinal Chemistry: A Comprehensive Bibliometric Analysis.","authors":"Yanhua Wang, Tongxin Guan, Dongyu Xu, Mingyan Liu, Zhichang Zhang","doi":"10.2174/011570159X384988250430093924","DOIUrl":"https://doi.org/10.2174/011570159X384988250430093924","url":null,"abstract":"<p><strong>Introduction: </strong>In the medicinal chemistry (MC) field, artificial intelligence (AI) has been used to establish quantitative structure-activity relationship (QSAR) classification models, virtual screening, drug discovery, drug design, and so on. In this investigation, MC AI studies (AI-MC) (from 2001-2023) underwent quantitative and qualitative modeling analyses.</p><p><strong>Methods: </strong>Using a hybrid research strategy incorporating content analyses and bibliometric methods, we retrospectively analysed the AI-MC literature using a bibliometrix package (R software) combined with CiteSpace V and VOSviewer programs.</p><p><strong>Results: </strong>Between 2001 and 2023, AI-MC articles were published in 92 countries or regions, with China and the United States leading in the number of publications. Also, 196 affiliations were added to AI-MC research; the CHINESE ACADEMY OF SCIENCES contributed the most. Reference clusters were categorized as follows: (1) QSAR, (2) virtual screening, (3) drug discovery, (4) drug design. Predictive model(2020-2021), molecular fingerprints (2021-2023) and scoring function (2021-2023) reflected research frontier keywords. As we look to the future, the ongoing progress and innovation in technology herald the promising development of multimodal and large language models (LLMs) within the realm of MC.</p><p><strong>Conclusions: </strong>We comprehensively characterized the AI-MC field and determined future trends and hotspots. Importantly, we provided a dynamic oversight of the AI-MC literature and identified key upcoming research areas.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076453","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":"Research Trends and Knowledge Atlas of Radiotherapy-Related Cognitive Impairment: A Bibliometric Analysis.","authors":"Yaqian Tan, Qi Song, Siyuan Gao","doi":"10.2174/011570159X368986250415105149","DOIUrl":"https://doi.org/10.2174/011570159X368986250415105149","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is one of the main therapeutic methods for tumors, and radiation- related cognitive impairment has attracted increasing attention. The purpose of this study was to explore the research prospects in the field of radiotherapy-associated cognitive decline through bibliometric analysis.</p><p><strong>Methods: </strong>Literature on radiotherapy-related cognitive impairment published during 2004-2023 were extracted from the Web of Science Core Collection database. VOSviewer and R-bibliometrix were utilized to perform bibliometric analysis.</p><p><strong>Results: </strong>A total of 8,365 publications were retrieved from the database. The United States emerged as the leading country in this research field, with St. Jude Children's Research Hospital identified as the most productive institution. Thomas E. Merchant was the most prolific author in this field, while Charles L. Limoli was the most frequently cited scholar. The research hotspots have gradually shifted from cognitive function and outcome measurement to the development of new therapy models.</p><p><strong>Conclusion: </strong>This study comprehensively examined the research hotspots and knowledge atlas of radiotherapy- related cognitive decline from a bibliometric perspective. Our results would assist scholars in identifying potential collaborators and significant literature in this field while also providing valuable guidance for future research directions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062628","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":"Excessive Urinary p75ecd is a Potential Indicator of Amyotrophic Lateral Sclerosis: An American Cohort Study.","authors":"Swati Dhasmana, Anupam Dhasmana, Sheema Khan, Acharan S Narula, Shafiul Haque, Murali M Yallapu, Subhash C Chauhan","doi":"10.2174/011570159X352364250212035802","DOIUrl":"https://doi.org/10.2174/011570159X352364250212035802","url":null,"abstract":"<p><strong>Introduction: </strong>Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and rapidly progressive neurodegenerative disease. At present, neurofilament light (NFL) and phosphorylated neurofilament heavy (pNfH) proteins in biological fluids are commonly known prognostic biomarkers, but their levels stabilize over time. Thus, there is a critical gap in the field to identify unique biomarkers that can aid disease diagnosis, progression and monitoring the therapy response.</p><p><strong>Aim: </strong>To evaluate the presence of extracellular domain of p75 (p75ecd) in urine of ALS patients and healthy control volunteers in the North American cohort.</p><p><strong>Method: </strong>An enzyme-linked immunoassay (ELISA) and creatinine assay was used to determine the levels of p75ecd and creatinine in the urine of ALS patients and healthy control volunteers respectively. This assay demonstrated clear discrimination in the levels of the p75ecd in the urine samples of ALS patients as compared to healthy individuals.</p><p><strong>Results: </strong>It was found that the concentration of p75ecd in ALS samples was significantly higher than that of healthy controls group. Additionally, high p75ecd levels were segregated with respect to age, sex, family history, occupation and drug treatment, medication status. Moreover, we observed differential expression patterns among the different stages of the disease. Our results followed the pattern that was observed in the Chinese, and Australian cohort.</p><p><strong>Conclusion: </strong>Altogether, our results indicate that the development of an efficient system for the detection of elevated levels of p75ecd in the urine could serve as a useful modality for early ALS diagnosis, disease progression, and monitoring the effectiveness of therapeutic interventions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982659","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":"Hydroxychloroquine Prevents High-altitude Cerebral Edema by Inhibiting Endothelial Claudin-5 Autophagic Degradation.","authors":"Yan Xue, Baolan Wan, Zhen Wang, Zhiwei Wang, Dongzhi Wang, Wanping Yang, Xueting Wang, Li Zhu","doi":"10.2174/011570159X371235250417051313","DOIUrl":"https://doi.org/10.2174/011570159X371235250417051313","url":null,"abstract":"<p><strong>Background: </strong>High-altitude cerebral edema (HACE) is a serious condition caused by pro-longed hypobaric hypoxia (HH). Autophagic degradation of Claudin-5 plays a crucial role in HH-induced blood-brain barrier (BBB) damage. Hydroxychloroquine (HCQ), a lysosomal inhibitor used in autophagy treatment, reduces inflammation and BBB damage in traumatic brain injury. However, its effectiveness in preventing HACE is still unknown.</p><p><strong>Methods: </strong>C57BL/6J mice were treated with HCQ and exposed to HH for 24 hrs to study BBB integ-rity. We evaluated BBB disruption via brain water content, Evans blue, and FITC-dextran assays. Changes in tight junctions (TJs) of cerebrovascular endothelial cells were analyzed using electron microscopy and immunofluorescence. Western blotting quantified autophagy protein levels in brain tissue. Hypoxia-mimetic in vitro models were used to explore HCQ's effects on TJs and BBB per-meability, confirmed by various assays, including immunofluorescence, electron microscopy, and Western blotting.</p><p><strong>Results: </strong>HCQ significantly mitigated rapamycin-induced autophagy and Claudin-5 degradation. Pro-longed hypoxia exposure promoted lysosomal degradation of Claudin-5, increasing endothelial cell permeability. HCQ inhibited autophagy in bEnd.3 cells via the PI3K-Akt-mTOR and Erk pathway, reducing hypoxia-induced Claudin-5 down-regulation. In mice, HH exposure increased brain au-tophagy, damaging the vascular endothelial TJs and subsequently increasing endothelial permeabil-ity. Pretreatment with HCQ significantly reduced the level of autophagy in the brains of HH-exposed mice, thereby mitigating the HH-induced damage to vascular TJs, alleviating the downregulation of Claudin-5, and enhancing endothelial integrity.</p><p><strong>Conclusion: </strong>HCQ effectively prevented HACE by inhibiting HH-induced Claudin-5 membrane ex-pression downregulation, thus mitigating BBB damage and brain water content increase in HH-exposed mice.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983905","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 Mechanisms and Application Prospects of Astrocyte Reprogramming into Neurons in Central Nervous System Diseases.","authors":"Rongxing Qin, Xinyu Lai, Wei Xu, Qingchun Qin, Xiaojun Liang, Minshan Xie, Li Chen","doi":"10.2174/011570159X379061250415094751","DOIUrl":"https://doi.org/10.2174/011570159X379061250415094751","url":null,"abstract":"<p><p>Central nervous system (CNS) diseases, including ischemic stroke (IS), Alzheimer's disease (AD), and Parkinson's disease (PD), are leading causes of global disability and mortality, characterized by progressive neuronal loss and irreversible neural circuit damage. Despite advances in understanding their pathophysiology, therapeutic options remain limited due to the complexity of disease mechanisms and challenges in delivering treatments across the blood-brain barrier (BBB). In this context, astrocyte reprogramming has emerged as a groundbreaking strategy for neural repair. By leveraging the plasticity of astrocytes, researchers have demonstrated the potential to convert these glial cells into functional neurons, offering a novel approach to replenish lost neurons and restore neural function. This review explores the latest advancements in astrocyte reprogramming, focusing on transcription factor-mediated, miRNA-induced, and small molecule-based strategies, as well as the molecular mechanisms underlying this process. We also discuss the therapeutic potential of astrocyte reprogramming in CNS diseases, including IS, AD, PD, and other neurodegenerative disorders, while addressing the challenges and future directions for clinical translation. Through a systematic analysis of recent studies, this review highlights the promise of astrocyte reprogramming as a transformative therapeutic strategy for CNS repair, providing new hope for patients with debilitating neurological conditions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983168","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":"Vasoactive Intestinal Peptide: A Neuropeptide that Plays an Important Role in Parkinson's Disease.","authors":"Wenhui Fan, Ke Li, Ruohua Wang, Rongsha Chen, Yiben Liu, Zhongshan Yang, Ninghui Zhao, Jinyuan Yan","doi":"10.2174/011570159X374501250425045109","DOIUrl":"https://doi.org/10.2174/011570159X374501250425045109","url":null,"abstract":"<p><p>Parkinson's disease (PD) is primarily characterized by rigidity and tremor, which are pathologically associated with α -synuclein aggregation, especially in dopaminergic neurons in the midbrain. As it is a multi-factorial disease, there are currently no effective treatments but only mitigative therapies. Vasoactive intestinal peptide (VIP), a 28-amino acid neurotransmitter, is widely distributed in both the central and peripheral nervous system with a broad biological effect. Studies have shown that VIP exhibits anti-inflammatory, antioxidant, and anti-apoptotic effects and regulates glial cells and immune cells to protect and repair nerve cells. This article reviews the research progress of VIP as a brain-gut peptide in the treatment of PD and possible future research directions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972965","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":"Nitric Oxide Metabolite Improves Cognitive Impairment by Reducing the Loss of Parvalbumin Inhibitory Interneurons in a Novel Mouse Model of Vascular Dementia.","authors":"Xiaorong Zhang, Lin Cheng, Seung-Bum Yang, Moon-Se Jin, Quanyu Piao, Dae-Weung Kim, Min-Sun Kim","doi":"10.2174/011570159X356939250306075324","DOIUrl":"https://doi.org/10.2174/011570159X356939250306075324","url":null,"abstract":"<p><strong>Background: </strong>This work aimed to develop a new and simple method to establish a mouse model of vascular dementia (VD). We investigated whether a new nitric oxide metabolite in the botanical mixture (a NO-donating botanical mixture, NOBM) improved learning and memory in mice that underwent bilateral carotid artery stenosis (BCAS).</p><p><strong>Method: </strong>C57BL/6N mice received the NOBM orally (0.1 mL twice a day) after BCAS, from days 1 to 28. We assessed spatial memory using the Y maze and place recognition tests at 1 week and 4 weeks after the induction of BCAS. We quantified the parvalbumin protein in the cortex and hippocampus at 1 week and 4 weeks. We also quantified expression levels of neuronal nuclei, brainderived neurotrophic factor, glial fibrillary acidic protein, and the number of dead neurons performed Fluoro-Jade B staining 31 days after BCAS.</p><p><strong>Results: </strong>NOBM significantly improved learning and memory behaviour in BCAS mice. Immunohistochemistry staining and Western blotting data showed a significantly higher protein expression of parvalbumin in the cortex and hippocampus of NOBM-treated BCAS animals, especially in the early stage of BCAS. Moreover, NOBM reduces neuronal loss in the cortex and reduces neuroinflammation and oxidative stress. The observed effect suggests that the NOBM reduced the loss of parvalbumin inhibitory interneurons in the early stage of VD and inhibited neuroinflammation in the VD mice model.</p><p><strong>Conclusion: </strong>Our results reveal a potential neuroprotective and therapeutic use of NOBM for cognitive dysfunction associated with cerebral hypoperfusion in a mouse model of VD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977666","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":"Therapeutic Benefits of Bioactive Compounds in Brain Disorders.","authors":"Arianna Vignini","doi":"10.2174/011570159X404730250422071304","DOIUrl":"https://doi.org/10.2174/011570159X404730250422071304","url":null,"abstract":"","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972962","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}