Current Neuropharmacology最新文献

{"title":"The Extract of <i>Siegesbeckia orientalis</i> L. Reverses Pro-inflammatory Status of Microglia for Neuroprotection Following Ischemic Stroke in Mice.","authors":"Liu Bowen, Wan Bingjie, Zhao Xinyue, Zhao Yonghua, Yu Hua, Jiang Xuhong, Zheng Yanrong, Xu Yun","doi":"10.2174/011570159X349127241214045611","DOIUrl":"https://doi.org/10.2174/011570159X349127241214045611","url":null,"abstract":"<p><strong>Background: </strong><i>Siegesbeckia orientalis L. </i> (SO) is a traditional Chinese herbal medicine commonly used for inflammatory diseases. In ancient, SO is applied for stroke, but mechanisms have not been clear. The purpose is to investigate whether SO exerts neuroprotective effects by reducing microglia-related inflammatory injury after focal cerebral ischemia/reperfusion (I/R).</p><p><strong>Methods: </strong>SO was extracted using 50% ethanol and quality control was performed by Waters ACQUITY- UPLC CLASS system. The focal cerebral I/R model was established in mice, neurological functions, weight loss and infarct volume was evaluated. Microglial status in penumbra was monitored by immunofluorescence staining and morphology. Mouse primary microglia was subjected to lipopolysaccharide stimulation for triggering inflammatory response, meanwhile microglia-neuron co-culture model was established in vitro. Apoptosis and pyroptosis for neurons were demonstrated using TUNEL assay, western blot and ELISA. Inflammatory cytokines were detected by qPCR and ELISA.</p><p><strong>Results: </strong>SO treatment reduced infarct volume, improved neurological functions, lessened neuronal apoptosis and pyroptosis shown by increased Bcl-2/Bax ratio, decreased cleaved Caspase-3 and suppressed NLRP3/Caspase-1/GSDMD expression after I/R. Moreover, microglial status from proinflammation to anti-inflammation was characterized by morphological change and increasing percentage of CD206/Iba1 positive cells after SO treatment. Additionally, SO decreased TLR4 and nuclear- located p65 expression, suppressed IL-1β, IL-6, IL-18, and TNF-α, but increased IL-10 secretion both in vivo and vitro.</p><p><strong>Conclusion: </strong>SO reverses pro-inflammatory status of microglia as evidenced by suppression of TLR4/NF-κB cascade, down-regulation of pro-inflammatory cytokines and up-regulation of antiinflammatory cytokines, which contributes to its neuroprotective against neuronal pyroptosis and apoptosis after ischemic stroke.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989784","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":"Microglia-Astrocyte Crosstalk in Post-Stroke Neuroinflammation: Mechanisms and Therapeutic Strategies.","authors":"Tong Shang, Binglin Kuang, Yaxin Shang, Wei Zou","doi":"10.2174/011570159X350639250403072430","DOIUrl":"https://doi.org/10.2174/011570159X350639250403072430","url":null,"abstract":"<p><p>Stroke is a leading cause of severe disability and mortality worldwide. Glial cells in the central nervous system (CNS) not only provide nutritional support but also play crucial roles in the inflammatory response. Microglia and astrocytes, integral components of the innate immune system, are involved in all stages of stroke and are active participants in inducing post-stroke neuroinflammation. Recent studies have increasingly focused on the potential crosstalk between microglia and astrocytes, identifying it as a promising area for understanding the pathogenesis and therapeutic mechanisms of CNS inflammatory diseases. These cells not only undergo dynamic phenotypic changes but also establish an intimate two-way dialogue by releasing various signaling molecules. This review paper elucidates the spatiotemporal dynamics of microglia and astrocytes in post-stroke neuroinflammation and highlights interaction pathways and potential therapeutic strategies for stroke.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989685","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":"Multimodal Prediction and Intervention of Internet Gaming Disorder.","authors":"Qinghua He, Hanlin Cheng","doi":"10.2174/011570159X390484250417063434","DOIUrl":"https://doi.org/10.2174/011570159X390484250417063434","url":null,"abstract":"","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989782","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 Role and Mechanism of Estrogen in Perimenopausal Depression.","authors":"Yaqi Liu, Xiying Fu, Boyun Guan, Ranji Cui, Wei Yang","doi":"10.2174/011570159X371863250327073835","DOIUrl":"https://doi.org/10.2174/011570159X371863250327073835","url":null,"abstract":"<p><p>Depression is a severe psychiatric disorder characterized by high prevalence rates, elevated suicide risks, and significant relapse rates. Women, particularly during the perimenopausal period, are more vulnerable to developing depression. Fluctuations in estrogen levels during perimenopause can heighten a woman's sensitivity to psychosocial stress. Clinical trials have demonstrated the short-term antidepressant efficacy of estradiol in perimenopausal women. However, the precise mechanisms through which estrogen influences mood disorders during perimenopause remain unclear. This review summarizes the risk factors associated with perimenopausal depression (PMD), examines current research on estrogen therapy, and explores the potential mechanisms and related pathological processes involved in estrogen's role in treating depression. Understanding how estrogen mitigates depressive symptoms in perimenopausal women may help reduce the morbidity and mortality associated with PMD while also alleviating its socioeconomic burden.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970485","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 Comprehensive Understanding of Psychomotor Agitation: From Causes to Hospital Care.","authors":"Antonio Del Casale, Jan Francesco Arena, Christian Napoli, Fabiano Grassi, Serena Mancino, Cristina Di Legge, Barbara Adriani, Giovanna Parmigiani, Alessandro Vento, Giorgio Veneziani, Carlo Lai, Stefano Ferracuti","doi":"10.2174/011570159X340145250109080932","DOIUrl":"https://doi.org/10.2174/011570159X340145250109080932","url":null,"abstract":"<p><p>Psychomotor agitation is a syndrome characterized by abnormal psychic and motor activation, with a concrete possibility of escalation to aggression or violence. It represents a frequent reason for attending emergency departments and can stem from various organic conditions and mental disorders. In emergency settings, prompt identification of the possible underlying cause and optimal management are crucial to ensure the safety of both patients and healthcare providers. However, current management strategies are based on evidence focused on too specific clinical contexts or aspects of patient care. This narrative review aims to consolidate available evidence on clinical-diagnostic evaluation, severity assessment, patient-specific interventions, and hospital management. Patients should always be approached using de-escalation techniques while providing a rapid and systematic assessment of the key differential elements between organic and psychiatric causes. Pharmacological interventions are recommended as secondary measures to ensure safety and should be directed at facilitating the therapeutic relationship. Physical restraints and seclusion should be used only as a last resort, for the shortest duration, and under strict medical supervision. There is a pressing need for the systematic organization of evidence into effective guidelines to optimize the clinical approach to psychomotor agitation, improving both patient outcomes and safety in emergency settings.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973096","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":"Altered GABAergic Homeostasis in the Striatum of Dopamine Transporter Knockout Rats.","authors":"Giorgia Targa, Beatrice Rizzi, Francesca Mottarlini, Raul R Gainetdinov, Damiana Leo, Fabio Fumagalli, Lucia Caffino","doi":"10.2174/011570159X370747250404060428","DOIUrl":"https://doi.org/10.2174/011570159X370747250404060428","url":null,"abstract":"<p><strong>Background: </strong>It is now widely established that dopamine, despite its nature as a slowacting biogenic monoamine, modulates fast neurotransmitters such as GABA. However, the mechanism through which this occurs still needs to be fully elucidated. The dopamine transporter (DAT) is the primary regulator of dopamine homeostasis, controlling extracellular levels of dopamine as well as its storage in vesicles.</p><p><strong>Methods: </strong>Here, we took advantage of the availability of dopamine transporter knockout (DAT-/-) rats, which provide a unique opportunity to investigate the response of the GABAergic system under hyperactivity of the dopaminergic system, a condition found in different disorders of the Central Nervous System. The expression levels of GABAergic markers have been evaluated by means of western blot in the whole homogenate, cytosolic fraction, and post-synaptic density of the striatum of male DAT-/- rats.</p><p><strong>Results: </strong>We found a widespread down-regulation of GABAergic markers in the striatum of DAT-/- rats. Our data show that DA overactivity critically reorganizes the striatal GABAergic synapse in a way that GABA neurotransmission appears to be toned down. Such changes are equally distributed among proteins regulating GABA synthesis (GAD67), release (vGAT) and reuptake (GAT1, GAT3). It also involve the main subunits of GABA receptors (GABA-A a1, a2, b1; GABA-B R1), their anchoring proteins (Gephyrin) and adhesion molecules (Neuroligin-2).</p><p><strong>Conclusion: </strong>Taken together, such changes paint a picture showing a compromised integrity of the striatal GABAergic system under conditions of functional hyperdopaminergia, which may be of interest for several disorders of the central nervous system.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978493","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":"Microbiota-gut-brain axis: Novel Potential Pathways for Developing Antiepileptogenic Drugs.","authors":"Huifeng Li, Huanling Lai, Yue Xing, Shangnan Zou, Xiaofeng Yang","doi":"10.2174/1570159X23666250414094040","DOIUrl":"https://doi.org/10.2174/1570159X23666250414094040","url":null,"abstract":"<p><p>The treatment of epilepsy remains imperfect due to a lack of understanding of its pathogenesis. Although antiseizure medications can control most seizures, up to 30% of patients experience uncontrolled seizures, leading to refractory epilepsy. Therefore, elucidating the pathogenesis of epilepsy and exploring new avenues to design antiepileptic drugs may improve epilepsy treatment. Recent studies have identified an imbalance of the gut microbiota (GM) in both patients with epilepsy and various animal models of epilepsy. In response to this phenomenon, an increasing number of studies have focused on controlling seizures by regulating GM homeostasis, utilizing methods such as dietary restrictions, fecal microbiota transplantation, and the use of prebiotics. Surprisingly, these interventions have shown promising antiepileptic effects, suggesting that GM, through the regulatory role of the microbiota-gut-brain axis (gut-brain axis), may emerge as a novel strategy for treating epilepsy. This review aims to discuss the research progress on the relationship between GM and epilepsy, incorporating the latest clinical studies and animal experiments. We will specifically concentrate on the potential key role of the gut-brain axis in epileptogenesis, epilepsy development, and outcomes of epilepsy. Through a detailed analysis of the underlying mechanisms of the gut-brain axis, we aim to provide a more comprehensive perspective on understanding the pathophysiology of epilepsy and lay the groundwork for the development of new antiepileptic drugs in the future.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961883","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":"Photodynamic and Photothermal Therapies using Nanotechnology Approach in Alzheimer's Disease.","authors":"Büşra Öztürk, Huriye Demir, Mine Silindir Günay, Yagmur Akdag, Selma Sahin, Tugba Gulsun","doi":"10.2174/011570159X370790250317045223","DOIUrl":"https://doi.org/10.2174/011570159X370790250317045223","url":null,"abstract":"<p><p>Alzheimer's disease is a neurodegenerative disease that impairs cognitive function. The incidence of Alzheimer's disease increases with the increase in the elderly population. Although the clear pathogenesis of Alzheimer's disease is not yet known, the formation of amyloid plaques and tau fibrils, diminished acetylcholine levels, and increased inflammation can be observed in patients. Alzheimer's disease, whose pathogenesis is not fully demonstrated, cannot be treated radically. Since it has been observed that only pharmacological treatment alone isn't sufficient, alternative approaches have become essential. Among these approaches, nanocarriers greatly facilitate the transport of drugs since the blood-brain barrier is an important obstacle to the penetration of drugs into the brain. Photosensitizers trigger activation after exposure to near-infrared radiation light of a suitable wavelength or laser light, resulting in the selective destruction of Aβ plaques. Photodynamic therapy and photothermal therapy have been investigated for their potential to inhibit Aβ plaques through photosensitizers. By encapsulating photosensitizers in nanocarriers, the limitations of photosensitizers can be overcome. By using these photosensitizers, near-infrared radiation fluorescence imaging can be used as a theranostic. In this review, potential treatment options for photodynamic therapy and photothermal therapy for Alzheimer's disease are summarised, and a simultaneous or combined approach is discussed, taking into account potential nanotheranostics.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994104","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":"Potential Benefits of Quercetin through P2X7 Modulation against Neuroinflammation in Alzheimer's Disease.","authors":"Matheus Chimelo Bianchini, Francini Franscescon, Adinei Abadio Soares, Vinicius Ansolin, Kailane Paula Pretto, Marcelo Lemos Vieira da Cunha, Débora Tavares de Resende E Silva","doi":"10.2174/011570159X355614250130100132","DOIUrl":"https://doi.org/10.2174/011570159X355614250130100132","url":null,"abstract":"<p><p>Alzheimer's disease is the leading cause of dementia worldwide. It belongs to the group of neurodegenerative ailments caused by the accumulation of extracellular β-amyloid plaques (Aβ) and intracellular neurofibrillary tau tangles, which damage brain tissue. One of the mechanisms proposed involves protein neurotoxicity and neuroinflammation through the purinergic system pathway. Several endogenous nucleotides, such as Adenosine 5'-triphosphate (ATP), are involved in cell signaling. High ATP levels can cause P2X7 receptor hyper-stimulation, resulting in an exacerbated inflammatory process and in apoptosis of cells. From this perspective, searching for new therapies becomes important to assist in the patient's treatment and quality of life. As a flavonoid with several properties, including anti-inflammatory activity, Quercetin may be an alternative to alleviate the damage and symptoms caused by Alzheimer's disease. Therefore, this review aims to examine the potential of Quercetin through P2X7 modulation against neuroinflammation in Alzheimer's disease, as it affects the P2X7 receptor by direct and indirect interactions, resulting in decreased inflammation levels. Therefore, we believe that Quercetin may have significant power in modulating the P2X7 receptor, demonstrating that the purinergic system has the potential to modulate neuroinflammation and can add to the treatment, reduce disease progression, and result in better prognoses. Furthermore, technological alternatives such as Quercetin micronization might improve its delivery to target tissues.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994322","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":"Anticholinesterases Traits Inbuilt in Buxaceae Plant Extracts against Alzheimer's Disease.","authors":"Jiri Patocka, Srishti Sharma, Zdenka Navratilova, Namrata Singh, Romana Jelinkova, Nigar Mehboob, Patrik Oleksak, Eugenie Nepovimova, Kamil Kuca","doi":"10.2174/1570159X23666250326091016","DOIUrl":"https://doi.org/10.2174/1570159X23666250326091016","url":null,"abstract":"<p><p>This review provides a comprehensive account of advances in the field of cholinesterase inhibitors isolated from the Buxaceae family. Naturally occurring anticholinesterases derived from plants are considered to be a potential source of new drug candidates for treating Alzheimer's disease (AD). AD is now universally accepted as an irreversible, incurable, and progressive neurological disorder. Initiating with memory impairment, propagating with cognitive deficit, and ultimately leading to death is the general pathway of AD. Lower level of acetylcholine in the brain is characterized as one of the prominent reasons for AD. The cholinergic hypothesis states that elevated levels of acetylcholine in the brain can alleviate symptoms of AD. Steroidal and terpenoidal alkaloids isolated from plants of the Buxaceae family have been reviewed here for their anticholinesterase activity. Most of them have shown in vitro inhibition of horse serum butyrylcholinesterase (BuChE, EC 3.1.1.7) and electric eel acetylcholinesterase (AChE, EC 3.1.1.8). Although the general consensus has concluded that cholinesterase inhibitors may alleviate AD symptoms but cannot cure the disease, new drugs are still being sought to improve the quality of life of AD patients. Steroidal and terpenoidal anticholinesterase alkaloids can prove to be a promising group of AChE inhibitors.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983913","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}