Current Neuropharmacology最新文献

{"title":"Atherosclerosis as a Neuroimmune and Neurovascular Disorder: Pharmacological Opportunities Beyond Lipid Lowering.","authors":"Francisco Epelde","doi":"10.2174/011570159X518272260820062846","DOIUrl":"https://doi.org/10.2174/011570159X518272260820062846","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Atherosclerosis is traditionally defined as a lipid-driven inflammatory disease of medium and large arteries, but vascular inflammation also interacts with immune, autonomic, metabolic, and brain vascular pathways. This narrative review synthesizes evidence supporting an artery-immune-brain framework and identifies pharmacological opportunities beyond lipid-lowering and antithrombotic therapy.</p><p><strong>Methods: </strong>A targeted narrative review was performed using PubMed/MEDLINE, Google Scholar, and publisher databases, with priority given to randomized trials, guidelines, meta-analyses, and high-quality translational studies. Evidence was interpreted in accordance with translational maturity, distinguishing established clinical evidence from mechanisms that remain preclinical, indirect, or hypothesis-generating.</p><p><strong>Results: </strong>Established evidence supports intensive lipid lowering, residual inflammatory-risk assessment, and selected anti-inflammatory and cardiometabolic strategies in atherosclerotic disease. Translational evidence further suggests that adventitial immune-neural niches, autonomic imbalance, trained immunity, gut-derived metabolites, vascular senescence, blood-brain barrier dysfunction, and neurovascular-unit injury may amplify vascular and cognitive risk. These mechanisms differ substantially in clinical readiness.</p><p><strong>Discussion: </strong>The artery-immune-brain model helps explain residual vascular risk that is not fully captured by LDL-C, luminal stenosis, or recurrent ischemic events alone. It also supports trial designs that combine vascular, inflammatory, neuroimaging, cognitive, safety, and health-economic endpoints.</p><p><strong>Conclusion: </strong>Atherosclerosis should be viewed as a lipid-inflammatory disease with clinically established vascular consequences, and additional neuroimmune and neurovascular mechanisms that are promising but require phenotype-specific validation before therapeutic translation.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012113","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":"Ayurveda Therapies as a Promising Therapy in Neurological Disorders: A Comprehensive Narrative on Current References and Future Prospects.","authors":"Shalini Vijayanna Tirumalapura, Virupaksha S Harave","doi":"10.2174/011570159X437342260817060936","DOIUrl":"https://doi.org/10.2174/011570159X437342260817060936","url":null,"abstract":"<p><strong>Introduction: </strong>Complementary and Alternative Medicine (CAM) systems, such as Ayurveda, are frequently used to treat somatic symptoms and rehabilitate neurological disorders across diverse populations. Ayurveda, an ancient system of medicine, is predominantly practiced in Asian countries. Neurological diseases are effectively managed through Ayurveda treatment modalities, with substantial published evidence supporting their efficacy. Ayurveda offers a holistic approach to disease treatment, thereby enhancing the quality of life and reducing disease recurrence. The aim of the current review is to comprehensively review the Neuroprotective and neuroplasticity potential of Ayurveda external therapies.</p><p><strong>Methods: </strong>This review is based on the published literature on clinical studies demonstrating the effectiveness of Ayurveda-based external therapies in the management of neurological disorders. The studies available in PubMed, Scopus, Google Scholar, Science Direct, and the Ayush Research Portal from January 2000 to January 2026 were considered. The potential mechanisms of these therapies in neurological disorders are analysed using evidence from studies that have used them either as standalone or in combination.</p><p><strong>Results: </strong>The search showed many clinical studies on diverse neurological disorders, with varied treatment regimens. However, the number of case study reports exceeded the number of actual clinical studies, which poses a potential limitation for concluding the topic.</p><p><strong>Conclusion: </strong>This review will facilitate further research and the wide application of these therapies in neurorehabilitation and management.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012096","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":"Impact of Truncated Neuregulin-1 Type III Overexpression on Retinal and Visual Function in Mice.","authors":"Nan Su, Christin Stuffert, Markus H Schwab, Weiqi Zhang, Peter Heiduschka, Mingyue Zhang","doi":"10.2174/011570159X428474260902053641","DOIUrl":"https://doi.org/10.2174/011570159X428474260902053641","url":null,"abstract":"<p><strong>Introduction: </strong>Schizophrenia commonly involves multiple abnormalities, such as visual processing deficits. Neuregulin-1 (Nrg1) is a pleiotropic growth and differentiation factor that signals to receptor tyrosine kinases of the ErbB family, which possess an epidermal growth factor (EGF)-like domain. Abnormal expression of Nrg1 has been observed in individuals with schizophrenia, and pathological changes in the retina have also been reported in this population, involving changes to structural, neurochemical, and physiological aspects. However, the underlying mechanisms responsible for these changes are still not fully understood.</p><p><strong>Methods: </strong>In our study, we utilized transgenic mouse lines overexpressing an HA-tagged truncated Nrg1 Type III variant (HA-Nrg1Gief) lacking the intracellular domain (ICD) using electroretinography (ERG), visual evoked potentials (VEP), immunohistochemistry, and synaptic recordings in the lateral geniculate nucleus (LGN).</p><p><strong>Results: </strong>The current studies revealed a significant amplitude reduction in the group of scotopic a- and b-wave responses in middle-aged mice. In old-aged mice, scotopic a-wave amplitudes were similar between groups, while b-wave group responses were significantly higher in wild-type mice. Scotopic ERG latencies were similar in both groups and at both ages. Scotopic VEP amplitudes were significantly higher in wild-type mice at middle age, whereas VEP amplitudes were significantly higher in transgenic mice in the old-aged mice. Retrograde labelling of retinal ganglion cells (RGCs) demonstrated a significant reduction in the number of RGCs in HA-Nrg1GIEF mice in both age groups. Changes in retinal marker expression and retinal vascular abnormalities were also detected in transgenic mice. In middle-aged transgenic mice, recording of the LGN revealed increased GABAergic transmission compared to wild-type mice.</p><p><strong>Discussion: </strong>These findings suggest that in this model abnormal Nrg1 signalling is associated with visual pathway abnormalities. The extent of disruption along the retinal and thalamocortical pathways may be modulated by age-related differences.</p><p><strong>Conclusions: </strong>Our results suggest that this experimental model may be useful for studying visual pathway abnormalities relevant to deficits observed in schizophrenia. However, the behavioural correlates were not assessed in the present study. This study is limited by the absence of behavioural assessments linking visual and synaptic alterations to schizophrenia-related phenotypes. In addition, the sample sizes for some results were modest, and we did not perform sex-stratified analyses, which may restrict the generalizability of our findings. Future studies with larger cohorts and corresponding behavioural tests will be needed to clarify the translational relevance of this model.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967077","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 Impact of Anticholinergic Burden on Cognitive Function and Adverse Events Among Patients with Parkinson's Disease: A Meta-Analysis.","authors":"Yu-Feng Wang, Ing-Jy Tseng, Chun-Fu Lin, Che-Hsuan Lin, Shu-Fen Liao, Yuan-Hung Wang, Hsun-Hua Lee","doi":"10.2174/011570159X464947260902052340","DOIUrl":"https://doi.org/10.2174/011570159X464947260902052340","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Anticholinergic burden, the cumulative effect of medications with anticholinergic properties, is associated with cognitive decline and adverse health outcomes in older adults. In Parkinson's disease, anticholinergic agents are commonly prescribed to manage both motor and nonmotor symptoms, resulting in increased cumulative exposure. Despite the clinical relevance of anticholinergic burden, its effects in Parkinson's disease remain insufficiently characterized. This systematic review and meta-analysis investigated the association between anticholinergic burden and adverse outcomes in patients with Parkinson's disease.</p><p><strong>Methods: </strong>Eligible studies compared increased versus decreased anticholinergic burden by using validated scoring systems. PubMed, Embase, the Cochrane Library, and Web of Science were comprehensively searched for relevant articles published until February 29, 2024.</p><p><strong>Results: </strong>Eight studies met the inclusion criteria. A higher anticholinergic burden was associated with higher risks of dementia (odds ratio [OR]: 1.71; 95% CI: 0.93 to 3.17) and cognitive decline (standardized mean difference: -0.71; 95% CI: -1.51 to 0.08), but these associations were nonsignificant. Subgroup analysis revealed a significant association between anticholinergic burden and dementia in European cohorts (OR: 2.91; 95% CI: 1.02 to 8.28). A higher anticholinergic burden was significantly associated with higher risks of fracture (OR: 1.53; 95% CI: 1.28 to 1.84) and emergency department visits (OR: 1.25; 95% CI: 1.15 to 1.36).</p><p><strong>Discussion: </strong>These findings suggest that an increased anticholinergic burden in Parkinson's disease leads to adverse cognitive and physical outcomes.</p><p><strong>Conclusion: </strong>Although some associations did not reach statistical significance, the results highlight the need for cautious prescribing practices and regular medication reviews in patients with Parkinson's disease.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966461","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":"Gene Therapy for Glaucoma: Overcoming Limitations of Traditional Therapeutics.","authors":"Yaqin Zhang, Xiaoyu Dong, Caiyan Zheng, Qin Liu, Jinlin Xia, Huan Qin, Kai Yao","doi":"10.2174/011570159X481516260902055448","DOIUrl":"https://doi.org/10.2174/011570159X481516260902055448","url":null,"abstract":"<p><p>Glaucoma is a chronic neurodegenerative disease characterized by the deterioration of the optic nerve and the progressive loss of retinal ganglion cells (RGCs), making it a leading cause of irreversible blindness worldwide. This neurodegenerative process is characterized by the apoptotic death of neurons whose axons constitute the optic nerve, leading to permanent visual field deficits. Although current standard-of-care therapies-including pharmacological, laser, and surgical interventions-mainly target reducing intraocular pressure (IOP), their clinical efficacy remains limited due to side effects, inconsistent outcomes, and a failure to halt neurodegeneration. Therefore, there is an urgent need for novel therapeutic frameworks that move beyond symptomatic pressure control toward molecular intervention. Gene therapy has become one of the most promising directions due to its ability to offer new perspectives on the future management of glaucoma. Viral vectors, such as adeno-associated virus (AAV), can deliver therapeutic payloads directly to ocular tissues, potentially enabling long-term transgene expression after a single administration. This review discusses the pathophysiology of glaucoma and the shortcomings of available therapies, highlighting opportunities for next-generation genetic treatments. We group the possible options of gene therapy into two different paths, which are to regulate the flow of aqueous humor through the trabecular meshwork and the ciliary body, and directly provide neuroprotection to RGCs. The former involves genetic modulation of the conventional outflow pathway to restore physiological homeostasis, while the latter focuses on enhancing neurons' intrinsic survival signals by expressing neurotrophic factors or anti-apoptotic genes. Importantly, this review uniquely integrates these molecular targets with appropriate animal models, providing a comprehensive strategic framework for translating genetic discoveries into clinical applications.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967049","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":"Unraveling Druggable Targets in Epileptogenesis: Recent Advances.","authors":"Yee Seng Lee, Ching Soong Khoo, Jaya Kumar, Alina Arulsamy","doi":"10.2174/011570159X476664260824091459","DOIUrl":"https://doi.org/10.2174/011570159X476664260824091459","url":null,"abstract":"<p><strong>Introduction: </strong>Afflicting 50 million people worldwide, epilepsy accounts for a sizeable burden among neurological diseases. Its progression, termed epileptogenesis, and the sole availability of medications with negligible effects against its clinical course in the market render epilepsy largely incurable. As studies illuminate the anti-epileptogenic properties of natural compounds and repurposed drugs in recent decades, the treatable potential of epilepsy is increasingly speculated.</p><p><strong>Methods: </strong>In this review, mechanistic roles of prospective anti-epileptogenic targets in driving disease progression are clarified through the lens of neuroinflammation, neural remodeling, and neuronal death. This discussion integrates in vivo, in vitro, and clinical therapeutic evidence from the last two decades of epilepsy research, spanning pharmacoresistant to traumatic subtypes. Drug efficacies and limitations are also evaluated.</p><p><strong>Results: </strong>Apart from the IL-1β/IL-1R1 and TLR4/HMGB1 axes, tight junction proteins are emerging as areas of growing attention in neuroinflammation. While mTOR and Wnt/β-catenin cascades are prime targets for neural remodeling, modulating genetic hypermethylatory patterns and extracellular matrix expression alleviates convulsive phenotypes. Apoptotic and endoplasmic reticulum-mediated cell deaths are also responsive to respective pharmacological treatments. Several drugs exemplify synergistic effects spanning multiple epileptogenic processes, but adverse complications accompany some.</p><p><strong>Discussion: </strong>The adoption of anti-epileptogenic drugs (AEGDs) in place of anti-seizure medications (ASMs) offers a substantial window of disease-modifying action during the latency period, providing a golden opportunity to delay disease progression and thereby optimize patients' care. Because observations are still largely preclinical, examples could serve as a launching point for translational research to enable timely delivery of anti-epileptogenic regimens.</p><p><strong>Conclusion: </strong>Neuroinflammation, neural remodeling, and neuronal death are key processes of epileptogenesis, providing a druggable framework for future anti-epileptogenic treatments.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966724","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":"Intercellular Communication: Novel Perspectives on Stroke Therapeutic Strategies.","authors":"Zhe Shen, Wei Wang, Dongdong Shi","doi":"10.2174/011570159X478707260827045800","DOIUrl":"https://doi.org/10.2174/011570159X478707260827045800","url":null,"abstract":"<p><p>Stroke is one of the leading causes of death and disability globally, with ischemic stroke comprising approximately 87% of all cases. Although reperfusion therapies such as tissue-type Plasminogen Activator (tPA) are currently available, their clinical utility is severely limited by narrow therapeutic time windows and the risk of hemorrhagic transformation. Recent advances have revealed that ischemic stroke is not merely a localized vascular occlusion but a systemic pathological event governed by the Neurovascular Unit (NVU), including neurons, glial cells (astrocytes and microglia), vascular cells (endothelial cells and pericytes), and peripheral immune cells. Therefore, understanding the alterations in these diverse cell types and their underlying mechanisms holds significant importance for developing effective treatments for stroke. This review integrates current knowledge on the complex intercellular communication mechanisms within the NVU and at its periphery. We discuss how the functional polarization of astrocytes (neurotoxic A1 vs. neuroprotective A2) and microglia (M1/M2 phenotypes) dictate neuronal fate and neuroinflammatory responses. Additionally, we describe NVU-mediated regulation of cerebral blood flow and BBB permeability, as well as the interplay between peripheral and central immune responses in the context of stroke. Furthermore, we highlight novel communication modalities, specifically exosomes, which shuttle miRNAs and proteins to modulate distal inflammation, and Tunneling Nanotubes (TNTs), which facilitate the direct intercellular transfer of vital organelles, such as mitochondria. These dynamic interactions represent critical nodes for therapeutic intervention. Taken together, targeting the interactions of intercellular communication represents a promising frontier for achieving comprehensive functional recovery after ischemic stroke.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966474","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 Microbiome-Gut-Brain Axis: Decoding the Molecular Dialogue for Next-Generation Neurotherapeutics.","authors":"Muhammad Shahid Nadeem, Shakilur Rahman, Bibi Nazia Murtaza, Mohammed Al-Zharani, Muhammad Afzal, Fahd A Nasr, Saima Iftikhar, Kamel Chaieb, Sami I Alzarea, Imran Kazmi","doi":"10.2174/011570159X491341260902051725","DOIUrl":"https://doi.org/10.2174/011570159X491341260902051725","url":null,"abstract":"<p><p>The human brain has traditionally been considered an isolated organ until the establishment of the microbiome-gut-brain axis (MGBA) overturned that concept. Based on recent reports, the present review provides confirmatory evidence that there is a complex communication in the MGBA that links the central nervous system with the resident microbial community of the gastrointestinal tract. A complex, highly sophisticated molecular dialogue involving immune and neuroinflammatory molecules, signaling via the vagus nerve and neural pathways, and key metabolic and endocrine routes facilitates cross-talk between the brain and the gut microbiome. Crucial microbial metabolites, such as bile acids and short-chain fatty acids (SCFAs), neurotransmitter release, and modulation of systemic inflammation are highlighted as primary mediators of gut-brain interactions. In recent times, research has shifted from establishing associations to elucidating precise mechanisms between brain physiology and the composition of the gut microbial community. Recent studies have emphasized linking specific bacterial taxa to neurological outcomes in Alzheimer's disease (AD), Parkinson's disease (PD), and autism spectrum disorder (ASD). Emerging therapeutic modalities such as engineered live biotherapeutics, next-generation psychobiotics, precision nutrition, and fecal microbiota transplantation are promising avenues for next-generation neurotherapeutics. However, the path to clinical translation is fraught with challenges, including methodological heterogeneity and reproducibility, establishing causality, and confounding host factors. This review concludes with a forward-looking roadmap that emphasizes multi-omics integration, standardization, human-relevant disease models, and personalized therapeutic strategies to decode the MGBA and exploit its full potential, which could revolutionize the treatment of brain disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966730","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":"An Atlas of Modifiers of Age at Onset in Huntington's Disease.","authors":"Linliu Peng, Zhao Chen, Linlin Wan, Zhe Long, Jian Hu, Siyu Ding, Lang He, Huirong Peng, Yuting Shi, Xuan Hou, Rong Qiu, Beisha Tang, Chunrong Wang, Hong Jiang","doi":"10.2174/011570159X489741260824093006","DOIUrl":"https://doi.org/10.2174/011570159X489741260824093006","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is a fatal neurodegenerative disorder lacking effective treatment. The relationship between modifiable factors and age at onset (AAO) in HD remains controversial and causally unconfirmed. Identifying causal modifiers of AAO is crucial for delaying onset and disease prevention.</p><p><strong>Method: </strong>This study conducted the first comprehensive Mendelian randomization (MR) analysis of AAO causal determinants in HD. We reviewed previous observational and MR studies and identified 36 potential modifiers, of which 26 with available genetic instrument were analyzed. Summary statistics for residual AAO were obtained from the largest GWAS by the GeM-HD Consortium. The inverse-variance weighted method served as the primary analysis, with multiple sensitivity tests for robustness. Multivariable MR evaluated independent effects of exposures.</p><p><strong>Results: </strong>Univariable MR identified 14 modifiers causally associated with AAO. Six previously reported factors were replicated, including telomere length, leisure screen time, coffee consumption and metabolism, smoking behaviors, diastolic blood pressure, and target effect of calcium channel blockers (CCBs). Eight novel modifiers were discovered, including education, economic status, adiposity distribution, appendicular lean mass, overall effects of CCBs, triglycerides, and target effect of lipid-lowering drugs and overall effects of statins. Multivariable MR confirmed eight independent factors: education, leisure screen time, coffee consumption, smoking behaviors, visceral adiposity, overall effects of CCBs, triglycerides, and overall effects of statin use. All associations were consistent across sensitivity analyses.</p><p><strong>Conclusions: </strong>These findings provide the most comprehensive causal landscape of AAO modifiers in HD to date, highlighting modifiable biological and lifestyle factors that may underpin future preventive or therapeutic interventions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967109","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 Dorsal Raphe Nucleus: A Critical Hub in the Neurocircuitry of General Anesthesia.","authors":"Anyin Wang, Hui Zhou, Xinghe Wang, Ye Liao, Can Li, Kunwei Wu","doi":"10.2174/011570159X490032260630163835","DOIUrl":"https://doi.org/10.2174/011570159X490032260630163835","url":null,"abstract":"<p><p>The dorsal raphe nucleus (DRN), the brain's primary source of serotonin, is a critical hub for regulating arousal, mood, pain, and sleep-wake cycles. Here we review what is currently known about how the DRN modulates general anesthesia. We focus on four neuronal groups, namely serotonergic, GABAergic, glutamatergic, and dopaminergic, and how they interact to shape induction and emergence. Serotonergic neurons, by promoting cortical arousal, are a key driver of anesthetic emergence; their activation accelerates recovery, while their inhibition deepens unconsciousness. GABAergic neurons provide potent local inhibition of the serotonergic system, a mechanism exploited by many anesthetic agents to induce and maintain hypnosis. Recent studies highlight functional heterogeneity within these populations, revealing that GABAergic neurons can either promote or constrain arousal depending on their projection targets, and serotonergic neurons produce opposing sleep-wake effects based on firing pattern. Glutamatergic neurons exhibit resistance to anesthetic suppression, while dopaminergic neurons encode salience and modulate pain perception. These parallel, non-serotonergic pathways expand the DRN's functional repertoire beyond its traditional serotonergic framework, and this mechanistic understanding has direct clinical implications. For patients with serotonergic disorders such as depression and anxiety, anesthetic responses often deviate from the usual pattern, so perioperative plans need to account for individual differences. Furthermore, the DRN presents a promising target for personalized anesthesia, where future strategies may leverage neuroimaging or genetic biomarkers to predict individual susceptibility and guide drug selection or novel neuromodulation therapies. Understanding the DRN at the circuit level could help translate basic neuroscience into clinical anesthetic practice and improve patient care.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944302","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}