Current Neuropharmacology最新文献

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Advances and Challenges in Traumatic Brain Injury from a Forensic Perspective. 从法医角度看外伤性脑损伤的进展与挑战。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-26 DOI: 10.2174/011570159X352125241031030110
Shu-Quan Zhao, Yan-Wei Shi, Xiao-Guang Wang, Ke Liu, Hu Zhao
{"title":"Advances and Challenges in Traumatic Brain Injury from a Forensic Perspective.","authors":"Shu-Quan Zhao, Yan-Wei Shi, Xiao-Guang Wang, Ke Liu, Hu Zhao","doi":"10.2174/011570159X352125241031030110","DOIUrl":"https://doi.org/10.2174/011570159X352125241031030110","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is one of the leading causes of death and disability. Animal and clinical studies of TBI have greatly changed the clinical practice of TBI with the development and application of new technologies. However, with the development of forensic science, legal issues related to TBI continue to emerge, and it is still far from satisfactory that the practical application of relevant research findings as legal evidence in court practice. This review discusses an overview of the latest progress of TBI through neuropathological changes, secondary injury mechanisms, postmortem neuroimaging, cognitive, emotional, and behavioral impairments, biomarkers, and the effects of toxins and drugs on brain injury from a forensic perspective. Meanwhile, we highlight the interpretability and limitations of findings on TBI in legal proceedings are ongoing challenges.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514980","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}
引用次数: 0
Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders. 小胶质细胞在生理状况和中枢神经系统疾病中的突触生成、突触修剪和突触可塑性中的作用。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-26 DOI: 10.2174/1570159X23666250225091729
Meizhen Xie, Tian Wang, Jiachun Feng, Di Ma, Liangshu Feng, Yulei Hao
{"title":"Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.","authors":"Meizhen Xie, Tian Wang, Jiachun Feng, Di Ma, Liangshu Feng, Yulei Hao","doi":"10.2174/1570159X23666250225091729","DOIUrl":"https://doi.org/10.2174/1570159X23666250225091729","url":null,"abstract":"<p><p>Microglia are resident immune cells in the brain that have been widely studied for their immune surveillance and phagocytosis. In recent years, the important role of microglia in synapse formation, elimination, and plasticity is gradually being recognized. Synapses are the main communication mode between neurons. They undergo constant changes in quantity and plasticity throughout the life cycle, which is the basis of learning and memory. Microglia are highly motile, branched forms that monitor the microenvironment of the central nervous system (CNS) and promote synapse formation and maturation. They recognize and phagocytose redundant synapses through specific phagocytosis receptors. Furthermore, microglia regulate synaptic plasticity by releasing various effectors. The roles of microglia on synapses ensure the proper function of neural networks. Synaptic dysfunction and microglia activation are common features in CNS disorders, such as Alzheimer's disease, Parkinson's disease, ischemic stroke, cerebral hemorrhage, traumatic brain injury, multiple sclerosis, and epilepsy. Highly heterogeneous microglia exhibit diverse functions in these diseases and participate in disease progression by exacerbating or inhibiting synaptic dysfunction, in addition to neuroimmune and inflammation. In this article, we summarize the role of microglia on synapses under physiological conditions and in CNS disorders. We highlight the possible mechanisms by which microglia regulate synapse function in CNS disorders and how this affects the progression of the diseases. We aim to explore potential therapeutic targets for CNS disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514981","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}
引用次数: 0
ISR Modulators in Neurological Diseases. 神经系统疾病中的ISR调节剂。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-24 DOI: 10.2174/011570159X361653250213114821
Alexander Pavlovich Kalinin, Ekaterina Sergeevna Zubkova, Mikhail Yuryevich Menshikov, Yelena Victorovna Parfyonova
{"title":"ISR Modulators in Neurological Diseases.","authors":"Alexander Pavlovich Kalinin, Ekaterina Sergeevna Zubkova, Mikhail Yuryevich Menshikov, Yelena Victorovna Parfyonova","doi":"10.2174/011570159X361653250213114821","DOIUrl":"https://doi.org/10.2174/011570159X361653250213114821","url":null,"abstract":"<p><p>The dysfunction of different cells lies in the pathogenesis of neurological diseases and is usually associated with cellular stress. Various stressors trigger the integrated stress response (ISR) signaling, whose highly conserved mechanism is primarily aimed at protecting a stress-exposed cell to cope as safely as possible with such stressful conditions. On the contrary, if a cell is unable to cope with excessive stress, the ISR can induce apoptosis. The ISR mechanism, whose main stage is the inhibition of translation machinery in favor of the synthesis of specific proteins, including the transcription factors ATF3, ATF4, CEBPA, and CEBPB, which function only as dimers and determine the uniqueness of the ISR response in each individual case, thus ensures different outcomes of the ISR. Inhibition of global protein synthesis is achieved through phosphorylation of eIF2α by PERK, HRI, PKR, or GCN2. To date, a number of compounds have been developed that modulate the ISR, including activators and inhibitors of the abovementioned ISR kinases as well as modulators of p-eIF2α dephosphorylation. They target different ISR stages, allowing a broad ISR modulation strategy. At the same time, there are no drugs that are both exceptionally safe and effective for the treatment of several neurological diseases, so there is an urgent need for new approaches to the treatment of these disorders. In this review, we represent ISR signaling as an important participant in the pathogenesis of neurological diseases. We also describe how various ISR modulators may become a part of future therapies for these diseases.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491158","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}
引用次数: 0
Synaptic Interactions Between Serotonergic and Dopaminergic Systems in Parkinson's Disease. 帕金森病中5 -羟色胺和多巴胺系统的突触相互作用。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-21 DOI: 10.2174/011570159X336597241217062042
Gioia Marino, Federica Campanelli, Giuseppina Natale, Maria De Carluccio, Federica Servillo, Veronica Ghiglieri, Paolo Calabresi
{"title":"Synaptic Interactions Between Serotonergic and Dopaminergic Systems in Parkinson's Disease.","authors":"Gioia Marino, Federica Campanelli, Giuseppina Natale, Maria De Carluccio, Federica Servillo, Veronica Ghiglieri, Paolo Calabresi","doi":"10.2174/011570159X336597241217062042","DOIUrl":"https://doi.org/10.2174/011570159X336597241217062042","url":null,"abstract":"<p><p>Since both serotonergic and dopaminergic afferents densely innervate many parts of the central nervous system, intact crosstalk between serotonin (5-HT) and dopamine (DA) transmission is essential for regulating synaptic plasticity in the striatum (STR), prefrontal cortex (PFC), and hippocampus (HPC).. Experimental models have provided strong evidence of a synergistic action of DA and 5-HT convergent release in PFC, HPC, and STR to modulate motor control, learning, and memory processes. In this review, we will discuss the mechanisms underlying the actions of agonists and antagonists of 5-HT and DA receptors on striatal synaptic plasticity in physiological conditions and Parkinson's disease (PD), a movement disorder in which an imbalance of these two neurotransmitter systems has been hypothesized. This review will also discuss the interactions between 5-HT and DA in PFC and HPC, with particular regard to the influence of this crosstalk on synaptic plasticity and learning. Finally, we will provide an overview of how stimulation or inhibition of DA and 5- HT receptors affects these neurotransmitter expression levels in the three brain regions of interest.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482476","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}
引用次数: 0
Epigenetic Mechanisms in the Pathophysiology and Progression of Epilepsy: A Comprehensive Review of Experimental and Clinical Studies. 癫痫的病理生理和进展中的表观遗传机制:实验和临床研究的综合综述。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-19 DOI: 10.2174/1570159X23666241220163832
Yinchao Li, Zhengwei Su, Ke Zhao, Xianyue Liu, Shuda Chen, Xiaofeng Yang, Liemin Zhou
{"title":"Epigenetic Mechanisms in the Pathophysiology and Progression of Epilepsy: A Comprehensive Review of Experimental and Clinical Studies.","authors":"Yinchao Li, Zhengwei Su, Ke Zhao, Xianyue Liu, Shuda Chen, Xiaofeng Yang, Liemin Zhou","doi":"10.2174/1570159X23666241220163832","DOIUrl":"https://doi.org/10.2174/1570159X23666241220163832","url":null,"abstract":"<p><p>Epilepsy is a prevalent neurological disorder that presents with a diverse range of clinical manifestations and etiologies influenced by both genetic and environmental factors. However, traditional genetic mechanisms alone are insufficient to fully elucidate the pathogenesis of epilepsy, highlighting the increasing importance of epigenetics in epilepsy research. Several studies have demonstrated that epigenetic mechanism play a pivotal role in the development and progression of epilepsy. This review provides a comprehensive overview of epigenetic regulation and its role in epilepsy. We emphasize the specific role of epigenetic regulation, including DNA methylation, non-coding RNA, and histone modification in the epilepsy. Finally, we discuss the potential applications of epigenetic regulation in the etiology research, drug development, and personalized therapy of epilepsy, along with the technical and theoretical challenges that need to be addressed in epigenetic research. Epigenetic mechanisms have emerged as a promising avenue for understanding the pathogenesis and treatment of epilepsy. However, to thoroughly grasp its potential implications for the clinical management of this disease, a deeper understanding of the role of epigenetics in TLE is essential. Therefore, further research is required to elucidate the specific epigenetic mechanisms involved in epilepsy, their interactions with other disease-related factors, and their potential as therapeutic targets. Such research could ultimately lead to the development of novel epigenetic-based therapies for epilepsy and other related neurological disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457183","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}
引用次数: 0
Beneficial and Detrimental Effects of Uric Acid on Alzheimer's Disease. 尿酸对阿尔茨海默病的有益和有害影响。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-18 DOI: 10.2174/011570159X349365250128072146
O V Tovchiga, I Inkielewicz-Stepniak
{"title":"Beneficial and Detrimental Effects of Uric Acid on Alzheimer's Disease.","authors":"O V Tovchiga, I Inkielewicz-Stepniak","doi":"10.2174/011570159X349365250128072146","DOIUrl":"https://doi.org/10.2174/011570159X349365250128072146","url":null,"abstract":"<p><p>The interconnection between brain function and hyperuricemia remains controversial since the available evidence indicates both the potent neuroprotective role of uric and its negative cardiovascular and metabolic effects, possible prooxidant activity. A mixed (protective and risk) effect of uric acid on neurological disorders was assumed. Among the neurodegenerative diseases, Alzheimer's disease remains the most prevalent, causes disability, and lacks highly effective treatments. Therefore, this review aims to delineate the beneficial and detrimental effects of uric acid on Alzheimer's disease. This can not only facilitate estimating the benefits and risks of urate-lowering or urate-increasing interventions in different conditions but also can enhance understanding of the molecular pathways associated with the protective role of uric acid, leading to the identification of new therapeutic targets for neuroprotection. Firstly, we addressed interconnections between UA and AD in different patients and population subgroups. Secondly, we analysed which differences can arise at the level of uric acid transport to the brain, its influence on BBB, and its presence in brain tissue and cerebrospinal fluid. Such aspects as xanthine oxidase interrelationship with the risk of cognitive impairment was elucidated, as well as the unexpected interconnection between uric acid exchange and the cholinergic system. Finally, an analysis was done of the beneficial and detrimental effects of uric acid on such targets of Alzheimer's disease pathogenesis as the amyloid-β pathway, proinflammatory markers, peroxynitrite scavenging, and other aspects of prooxidant-antioxidant status.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457181","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}
引用次数: 0
Quantification of [11C]ABP688 Binding to mGluR5 in Human Brain using Cerebellum as Reference Region: Biological Interpretation and Limitations. 以小脑为参照区定量测定人脑[11C]ABP688与mGluR5的结合:生物学解释和局限性
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-18 DOI: 10.2174/1570159X23666250127161855
Michele S Milella, Luciano Minuzzi, Chawki Benkelfat, Jean-Paul Soucy, Alexandre Kirlow, Esther Schirrmacher, Mark Angle, Jeroen A J Verhaeghe, Gassan Massarweh, Andrew J Reader, Antonio Aliaga, Jose Eduardo Peixoto-Santos, Marie-Christine Guiot, Eliane Kobayashi, Pedro Rosa-Neto, Marco Leyton
{"title":"Quantification of [11C]ABP688 Binding to mGluR5 in Human Brain using Cerebellum as Reference Region: Biological Interpretation and Limitations.","authors":"Michele S Milella, Luciano Minuzzi, Chawki Benkelfat, Jean-Paul Soucy, Alexandre Kirlow, Esther Schirrmacher, Mark Angle, Jeroen A J Verhaeghe, Gassan Massarweh, Andrew J Reader, Antonio Aliaga, Jose Eduardo Peixoto-Santos, Marie-Christine Guiot, Eliane Kobayashi, Pedro Rosa-Neto, Marco Leyton","doi":"10.2174/1570159X23666250127161855","DOIUrl":"https://doi.org/10.2174/1570159X23666250127161855","url":null,"abstract":"<p><strong>Introduction: </strong>In vitro data from primates provide conflicting evidence about the suitability of the cerebellum as a reference region for quantifying type 5 metabotropic glutamate receptor (mGluR5) binding parameters with positron emission tomography (PET).</p><p><strong>Methods: </strong>We first measured mGluR5 density in postmortem human cerebellum using [3H]ABP688 autoradiography (n=5) and immunohistochemistry (n=6). Next, in vivo experiments were conducted in healthy volunteers (n=6) using a high-resolution PET scanner (HRRT) to compare [11C]ABP688 binding potential (BPND) values obtained with reference tissue methods and the two-tissue compartment model vs. metabolite-corrected arterial input function.</p><p><strong>Results: </strong>The postmortem data showed that, relative to the hippocampus, the cerebellum had 35% less mGluR5 immunoreactivity and 94% fewer [3H]ABP688 binding sites. In vivo brain regional [11C]ABP688 BPND values using the cerebellum as a reference region were highly correlated with BPND values and distribution volumes derived by arterial input methods (R2 > 0.9).</p><p><strong>Conclusion: </strong>The scarce availability of cerebellar allosteric binding sites at autoradiography, compared to immunohistochemistry results, might reflect the presence of distinct mGluR5 isoforms or conformational state. Together with our PET data, these data support the proposition that [11C]ABP688 BPND using the cerebellum as a reference region provides accurate quantification of mGluR5 allosteric binding in vivo. Studies relying on this method could, therefore, be used in clinical populations, providing that stronger initial assumptions are met.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457229","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}
引用次数: 0
The Modulatory Effects of Anesthetics and Analgesics on Neurophysiological Monitoring and Underlying Mechanisms. 麻醉药和镇痛药对神经生理监测的调节作用及其机制。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-18 DOI: 10.2174/011570159X349119250127104107
Yu Leng, Yi Teng, Jin Liu, Xian Zou, Mengchan Ou, Tao Zhu, Peng Liang, Cheng Zhou
{"title":"The Modulatory Effects of Anesthetics and Analgesics on Neurophysiological Monitoring and Underlying Mechanisms.","authors":"Yu Leng, Yi Teng, Jin Liu, Xian Zou, Mengchan Ou, Tao Zhu, Peng Liang, Cheng Zhou","doi":"10.2174/011570159X349119250127104107","DOIUrl":"https://doi.org/10.2174/011570159X349119250127104107","url":null,"abstract":"<p><p>Intraoperative Neurophysiological Monitoring (IONM) is an indispensable surgical tool that offers invaluable insights into neurological function across a spectrum of anatomical areas. By comprehensively assessing the integrity of the brain, brainstem, spinal cord, cranial nerves, and peripheral nerves, IONM plays a pivotal role in guiding surgical decision-making and optimizing patient outcomes, particularly in the context of high-risk procedures. Intraoperative drugs, especially anesthetics and/or analgesics, differentially modulate neurophysiological monitoring, which remarkably affects the application of neurophysiological monitoring under specific conditions and indicates the neurobiological mechanisms of anesthetics/analgesics. This review will describe various neurophysiological modalities utilized in intraoperative procedures, each employing a wide variety of physiological principles; summarize the modulatory effects of anesthetics/analgesics on these neurophysiological monitoring parameters; and elucidate their underlying mechanisms, with a particular emphasis on evoked potentials. Insights gleaned from this review can inform strategies of anesthesia management for surgeries that require IONM and guide future investigations on the mechanisms of anesthesia/analgesia.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456658","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}
引用次数: 0
Effects of a Rosiridin against Rotenone-induced Rats' Model of Parkinson's Disease: In-vivo Study and in silico Molecular Modeling. 罗西瑞定对鱼藤酮诱导的大鼠帕金森病模型的影响:体内研究和硅分子模型。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-13 DOI: 10.2174/011570159X349553250126050134
Misbahuddin Rafeeq, Fahad A Al-Abbasi, Muhammad Afzal, Khalid Saad Alharbi, Ehssan Moglad, Salwa D Al-Qahtani, Hussam A Bukhari, Faisal Imam, Nadeem Sayyed, Imran Kazmi
{"title":"Effects of a Rosiridin against Rotenone-induced Rats' Model of Parkinson's Disease: In-vivo Study and in silico Molecular Modeling.","authors":"Misbahuddin Rafeeq, Fahad A Al-Abbasi, Muhammad Afzal, Khalid Saad Alharbi, Ehssan Moglad, Salwa D Al-Qahtani, Hussam A Bukhari, Faisal Imam, Nadeem Sayyed, Imran Kazmi","doi":"10.2174/011570159X349553250126050134","DOIUrl":"https://doi.org/10.2174/011570159X349553250126050134","url":null,"abstract":"<p><strong>Aim: </strong>The investigation aimed to study the outcome of rosiridin in Parkinson's disease (PD) induced by rotenone (ROT) in rodents.</p><p><strong>Methods: </strong>Rodents were randomized into IV groups and were induced with ROT followed by treatment with rosiridin. Group I-IV received saline as a vehicle, II-ROT (0.5 mg/kg S.C) for 28 consecutive days, III and IV- rosiridin 10 and 20 mg/kg orally with ROT. On completion of the experimental duration, behavioral investigations were carried out. Biochemical variables such as acetylcholinesterase (AChE), oxidative stress and antioxidants markers (Malondialdehyde-MDA, glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), anti-inflammatory (Interleukin-1 beta-IL-1β, IL-6, and tumor necrosis factor alpha-TNF-α), alteration in neurotransmitters (Serotonin-5-HT), norepinephrine, and dopamine-DA, along with metabolites such as 5-hydroxy indole acetic acid-5- HIAA),), mitochondrial complex I, II, IV, and caspase-3 activity were evaluated at the end of the experiment. Furthermore, molecular docking and dynamics were performed for target ligands.</p><p><strong>Results: </strong>Rosiridin significantly restored the level of AChE, oxidative stress and antioxidants markers (MDA, GSH, SOD, and CAT), anti-inflammatory (IL-1β, IL-6, and TNF-α), alteration in neurotransmitters, mitochondrial complex I, II, IV, and caspase-3 activity. Rosiridin has a favorable negative binding affinity to AChE (-8.99 kcal/mol). The results of the molecular dynamics simulations indicate that proteins undergo a substantial change in conformational dynamics when binding to rosiridin.</p><p><strong>Conclusion: </strong>In this study, rosiridin may exhibit neuroprotective properties against the Parkinson's model for treating PD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413716","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}
引用次数: 0
Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Hydrogen Sulfide-induced Ca2+ Entry and Nitric Oxide Production in Human Cerebrovascular Endothelium. 瞬时受体电位锚蛋白1 (TRPA1)介导硫化氢诱导的人脑血管内皮Ca2+进入和一氧化氮生成。
IF 4.8 2区 医学
Current Neuropharmacology Pub Date : 2025-02-13 DOI: 10.2174/011570159X349872250124124612
Teresa Soda, Valentina Brunetti, Giovambattista De Sarro, Gerardo Biella, Francesco Moccia, Roberto Berra-Romani, Giorgia Scarpellino
{"title":"Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Hydrogen Sulfide-induced Ca2+ Entry and Nitric Oxide Production in Human Cerebrovascular Endothelium.","authors":"Teresa Soda, Valentina Brunetti, Giovambattista De Sarro, Gerardo Biella, Francesco Moccia, Roberto Berra-Romani, Giorgia Scarpellino","doi":"10.2174/011570159X349872250124124612","DOIUrl":"https://doi.org/10.2174/011570159X349872250124124612","url":null,"abstract":"<p><strong>Introduction: </strong>The gasotransmitter hydrogen sulfide (H2S) modulates various brain functions, including neuron excitability, synaptic plasticity, and Ca2+ dynamics. Furthermore, H2S may stimulate nitric oxide (NO) release from cerebrovascular endothelial cells, thereby regulating NO-dependent endothelial functions, such as angiogenesis, vasorelaxation, and cerebral blood flow (CBF). However, the signaling pathway by which H2S induces NO release from cerebrovascular endothelial cells is still unclear.</p><p><strong>Methods: </strong>Herein, we exploited single-cell imaging of intracellular Ca2+, H2S, and NO levels to assess how H2S induces Ca2+-dependent NO release from the human cerebrovascular endothelial cell line, hCMEC/D3.</p><p><strong>Results: </strong>Administration of the H2S donor, sodium hydrosulfide (NaHS), induced a dose-dependent increase in (Ca2+)i only in the presence of extracellular Ca2+. NaHS-induced extracellular Ca2+ entry was mediated by the Ca2+-permeable TRPA1 channel, as shown by pharmacological and genetic manipulation of the TRPA1 protein. Furthermore, NaHS-dependent TRPA1 activation led to NO release that was abolished by buffering the concomitant increase in (Ca2+)i and inhibiting eNOS. Furthermore, the endothelial agonist, adenosine trisphosphate (ATP), caused a long-lasting elevation in (Ca2+)i that was driven by cystathionine γ-lyase (CSE)-dependent H2S production and by TRPA1 activation. Consistent with this, ATP-induced NO release was strongly reduced either by blocking CSE or by inhibiting TRPA1.</p><p><strong>Conclusion: </strong>These findings demonstrate for the time that H2S stimulates TRPA1 to induce NO production in human brain microvascular endothelial cells. Additionally, they show that this signaling pathway can be recruited by an endothelial agonist to modulate NO-dependent events at the human neurovascular unit.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413719","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}
引用次数: 0
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