Current Neuropharmacology最新文献

{"title":"MAPT Haplotype Variation and Alzheimer's Disease Risk: A Narrative Review with Focus on the Jordanian Population.","authors":"Alaa A A Aljabali, Almuthanna Alkaraki, Mohammad A Obeid","doi":"10.2174/011570159X371971250818110608","DOIUrl":"https://doi.org/10.2174/011570159X371971250818110608","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic variations in the microtubule-associated protein tau (MAPT) gene play a central role in Alzheimer's disease (AD) pathogenesis. Two major MAPT haplotypes, H1 and H2, show differential associations with tau expression and AD risk. However, data from Middle Eastern populations remain limited, restricting our understanding of population-specific disease susceptibility patterns and therapeutic responses.</p><p><strong>Methods: </strong>We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. Search terms included \"MAPT haplotype,\" \"Alzheimer's disease,\" \"H1 H2,\" \"tau pathology,\" and \"pharmacogenetics.\" We analyzed peer-reviewed articles published between 2000 and 2024, focusing on studies reporting haplotype frequencies, MAPT expression levels, APOE interactions, and clinical outcomes. This review synthesizes published data without generating new experimental results.</p><p><strong>Results: </strong>The H1 haplotype consistently associates with increased MAPT expression, tau accumulation, and elevated AD risk, particularly in APOE ε4 noncarriers. Conversely, the H2 haplotype appears protective, correlating with reduced tau burden and slower cognitive decline. Notably, recent reports reveal significant overrepresentation of the H2 haplotype in the Jordanian population compared to European and East Asian cohorts, where H2 frequency is substantially lower or absent. This distinct genetic architecture suggests altered regional AD risk profiles.</p><p><strong>Discussions: </strong>The elevated H2 frequency in Jordan represents a unique population-specific genetic signature that may influence regional AD susceptibility patterns. These findings challenge current risk models predominantly based on European populations and suggest the need for populationtailored approaches in neurodegenerative disease research. The naturally H2-enriched Jordanian cohort provides an exceptional opportunity to investigate protective mechanisms against tau pathology.</p><p><strong>Conclusion: </strong>MAPT haplotype distributions show significant population variation with important implications for AD risk assessment and therapeutic targeting. The high H2 frequency in Jordan warrants integration into personalized medicine frameworks and population-specific disease models, potentially informing more effective regional prevention and treatment strategies.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063642","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 of Gut Bacteria and Plasma Metabolites in Predicting Post-Stroke Depression in Patients with Acute Ischemic Stroke.","authors":"Lulu Wen, Tong Si, Chuming Yan, Huixin Shen, Wancheng Zheng, Meihong Xiu, Miao Qu","doi":"10.2174/011570159X390349250818115524","DOIUrl":"https://doi.org/10.2174/011570159X390349250818115524","url":null,"abstract":"<p><strong>Introduction: </strong>Early diagnosis of Post-Stroke Depression (PSD) is challenging. This study aimed to identify possible biomarkers in gut microbiota and plasma metabolites within 72 hours after Acute Ischemic Stroke (AIS) to predict PSD occurring 2 weeks later.</p><p><strong>Method: </strong>In this study, 86 patients with AIS were observed within 3 days of stroke onset and followed up for 2 weeks. We collected the feces and plasma within 72 hours of AIS onset for 16S rRNA sequencing and liquid chromatography-mass spectrometry analysis, respectively.</p><p><strong>Results: </strong>At the genus level, PSD patients at 2 weeks following a stroke had a higher relative abundance of Blautia, Eubacterium_hallii_group, Tyzzerella, and a lower abundance of Ellin6067, Massilia, Luedemannella, and Gemmataceae_others within 3 days of AIS onset. Meanwhile, when all metabolites in plasma collected within 72 hours after AIS onset were used to predict 2-week PSD, 31 altered metabolites were identified, of which 28 metabolites increased and 3 decreased, belonging predominantly to steroid and steroid derivatives, glycerophospholipids, fatty acyls, and prenol lipids. The Area Under the Curve (AUC) values for the clinical data, metabolic profiles, gut microbiota, and combined dataset were 0.664 (0.549,0.779), 0.739 (0.621, 0.857), 0.870 (0.781,0.960), and 0.955 (0.888,1), respectively.</p><p><strong>Discussion: </strong>Our study identified potential biomarkers from clinical data, gut bacteria, and plasma metabolites that contribute to PSD. Within 72 hours after AIS, combining these biomarkers from all three sources showed preliminary ability to predict PSD at 2 weeks. Metabolites had the highest contribution, followed by gut bacteria and clinical data.</p><p><strong>Conclusion: </strong>A biomarker panel including metabolites, gut microbiota, and clinical data within 72 hours after AIS onset could preliminarily predict PSD 2 weeks later.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063731","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 Decade of Research on C9orf72 in Frontotemporal Dementia (2014-2024): A Bibliometric Analysis of Global Trends and Hotspots.","authors":"Miao He, Sheng Zeng, Zhenchu Tang, Lixia Qin, Weiqian Yan, Chunyu Wang, Hainan Zhang, Zhao Chen, Zhe Long","doi":"10.2174/011570159X388118250808030811","DOIUrl":"https://doi.org/10.2174/011570159X388118250808030811","url":null,"abstract":"<p><strong>Introduction: </strong>Frontotemporal dementia (FTD) is the third most frequent dementia and the leading dementia subtype in individuals under 65. The discovery of C9orf72 (chromosome 9 open reading frame 72) GGGGCC abnormal expansion is a major genetic cause of both FTD and amyotrophic lateral sclerosis (ALS), linking these diseases along a clinicopathological spectrum. This study aimed to depict the research landscape of C9orf72 in FTD over the past decade, track emerging research hotspots, and provide insights into under-researched areas.</p><p><strong>Method: </strong>Based on the Web of Science database, a bibliometric analysis was conducted to explore publication trends, key contributors, funding sources, journal categories, co-authorship networks, and keyword co-occurrence, clustering, and bursts.</p><p><strong>Results: </strong>A total of 1,220 articles were identified, with sustained output of over 100 articles annually. The majority of contributions and funding support came from North America and Europe. Hot research themes included hexanucleotide repeats, nucleocytoplasmic transport, disease mechanisms, and therapeutic targets.</p><p><strong>Discussion: </strong>North America and Europe were highly productive, supported by higher regional prevalence, genetic burden, and robust funding. Ploy-GR in cerebrospinal fluid has emerged as a diagnostic biomarker. Pathogenic mechanisms remain complex, involving both gain- and loss-of-function effects. Metformin and antisense oligonucleotides were considered as potential therapeutics. Further research is needed in underrepresented populations and on the translational potential of emerging molecular targets.</p><p><strong>Conclusion: </strong>This study offers a comprehensive overview of current trends and future directions over the past decade in C9orf72-related FTD research, allowing researchers-particularly those new to the area-to quickly understand the current landscape.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999850","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-Neuron Interactions in Alzheimer's Disease.","authors":"Yujie Ma, Xinyue Wang, Minghuang Gao, Yeze Lin, Qini Chen, Hongyin Yang, Cong Yang, Qi Wang","doi":"10.2174/011570159X379539250807114252","DOIUrl":"https://doi.org/10.2174/011570159X379539250807114252","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive disease characterized by significant cognitive decline, posing a substantial threat to life. Neuronal loss and dysfunction are responsible for the cognitive decline and behavioral disturbances observed in AD. Microglia are increasingly recognized for shaping the fate of neurons. However, the role of microglia-neuron interaction in neuronal degeneration of AD remains largely unclear. This review discusses microglia-mediated excessive synaptic pruning and microglia-neuron metabolic coupling in the neuronal degeneration of AD. It also summarizes the role of microglia-neuron interactions in classical pathogenic hypotheses such as the amyloid cascade, tau protein, neuroinflammation, and metal ions. It is found that microglia can serve as protectors of neurons, yet they also exacerbate neuronal damage under stress stimulation. This bidirectional modulation of microglia-neuron interaction provides a novel direction for rescuing AD neurons.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946024","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":"Pharmacodynamics and Pharmacokinetics of Ublituximab Compared with Other Anti-Cd20 Monoclonal Antibodies for Multiple Sclerosis Treatment.","authors":"Monica Margoni, Luca Battistini, Diego Centonze, Roberto Furlan, Claudio Gasperini, Massimo Filippi","doi":"10.2174/011570159X392955250815095236","DOIUrl":"https://doi.org/10.2174/011570159X392955250815095236","url":null,"abstract":"<p><p>The therapeutic scenario for Multiple Sclerosis (MS) has expanded rapidly over the last few years. Among the available treatments, anti-CD20 monoclonal antibodies, including rituximab, ocrelizumab, ofatumumab, and ublituximab, have shown significant results in reducing disease activity and slowing progression, particularly in relapsing MS. The distinct mechanisms of action, including the pharmacokinetic and pharmacodynamic profiles as well as the immunogenicity of these drugs, require careful consideration to tailor treatment for individual patients. A comprehensive review of the literature was conducted by searching PubMed and evaluating key studies, trials, and congress abstracts related to the use of anti-CD20 monoclonal antibodies. The analysis focused on the pharmacokinetic and pharmacodynamic profiles, as well as the immunogenicity, of anti-CD20 therapies currently available, with particular emphasis on the recently approved ublituximab. Ocrelizumab is effective in both relapsing-remitting and primary-progressive MS, using Antibody- Dependent Cellular Cytotoxicity (ADCC) as its primary mechanism of action, with intravenous and subcutaneous administration options ensuring flexible treatment delivery. Ofatumumab depletes B-cells through enhanced complement-dependent cytotoxicity, offering convenient monthly subcutaneous self-administration. Ublituximab's unique glycoengineered fragment crystallizable region enhances ADCC, resulting in rapid B-cell depletion and potentially improving its safety profile. Ublituximab allows for a shorter infusion time without requiring post-infusion monitoring after the second dose, provided there have been no prior reactions. Understanding the characteristics of different anti-CD20 monoclonal antibodies is critical for optimizing treatment, enhancing patient outcomes, and minimizing treatment burden. Ublituximab represents a promising option, offering a shorter infusion time and higher ADCC activity, which complements existing treatments such as ocrelizumab and ofatumumab.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946044","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 Complex Interactions Mechanisms Linking PTSD and Chronic Diseases.","authors":"Celina Cavalcante Muniz Gomes, Joelson Germano Crispim, Michelle Melgarejo da Rosa","doi":"10.2174/011570159X392154250730072830","DOIUrl":"https://doi.org/10.2174/011570159X392154250730072830","url":null,"abstract":"<p><p>Post-traumatic stress disorder (PTSD) is a chronic and multifactorial psychiatric condition that is often underdiagnosed, particularly when associated with chronic diseases (CDs). These conditions arise from complex interactions among psychosocial, socioeconomic, epigenetic, immune, metabolic, and neurobiological factors. Current treatment options for PTSD and CDs, whether isolated or comorbid, remain suboptimal. Addressing the bidirectional relationship between PTSD and CDs is a pressing global public health challenge, necessitating a deeper understanding of the underlying molecular mechanisms. This review examines the interplay of stress-response and neurochemical factors in PTSD and CDs, highlighting how maladaptive stress responses to trauma can disrupt neurochemical pathways, contributing to the development of CDs, and vice versa. Despite this, a significant gap exists in the number of in vivo model studies that adequately mimic the comorbid symptoms of PTSD and CDs, hindering progress in elucidating shared cellular and molecular pathways. This limitation restricts therapeutic advancements. Therefore, a comprehensive understanding of the neurobiological dysfunctions in the brain and their crosstalk with the immune, cardiovascular, and endocrine systems is critical. Such insights will pave the way for individualized treatment strategies tailored to the unique profiles of patients with PTSD associated with CDs.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946017","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":"Structural and Functional Determinants of ARIA-H Risk in Anti-Amyloid Monoclonal Antibodies: A Comparative Mechanistic Framework for Alzheimer's Immunotherapy Development.","authors":"Dinghao An, Xinxin Zou, Yun Xu","doi":"10.2174/011570159X391766250806091602","DOIUrl":"https://doi.org/10.2174/011570159X391766250806091602","url":null,"abstract":"<p><strong>Introduction: </strong>Amyloid-beta-targeting monoclonal antibodies (mAbs) for Alzheimer's disease frequently induce amyloid-related imaging abnormalities with hemorrhage (ARIA-H), yet systematic comparisons of ARIA-H incidence across therapeutic agents remain limited. Post-approval research prioritizes dosing over mechanism, leaving unresolved whether ARIA-H variations originate from intrinsic mAb properties. We address two gaps: comparative ARIA-H risk stratification among clinically available/investigational mAbs, and elucidation of structural/functional features influencing ARIA-H susceptibility.</p><p><strong>Methods: </strong>A systematic comparison of seven mAbs (donanemab, aducanumab, bapineuzumab, lecanemab, gantenerumab, crenezumab, solanezumab) was conducted, analyzing clinical trial data and molecular characteristics.</p><p><strong>Results: </strong>ARIA-H incidence ranked as follows (highest to lowest): donanemab > aducanumab > bapineuzumab > lecanemab > gantenerumab > crenezumab > solanezumab. Five mAb-specific determinants emerged: (1) Types of Aβ Binding: Enhanced clearance of mature amyloid plaques correlated with elevated ARIA-H risk. (2) Polymer binding Affinity: Reduced small oligomer-binding capacity predicted higher ARIA-H incidence. (3) Epitope location: N-terminal-targeting mAbs showed greater ARIA-H incidence vs. mid/C-terminal binders. (4) Fc region structure: IgG4-based constructs showed higher ARIA-H incidence than IgG1 analogs. (5) Clearance kinetics: Rapid attainment of amyloid reduction thresholds amplified ARIA-H incidence.</p><p><strong>Discussion: </strong>We identify a risk hierarchy for ARIA-H among anti-Aβ mAbs and link specific mAb biophysical properties-Aβ binding type, affinity for soluble oligomers, epitope specificity, Fc structure, and plaque clearance dynamics-directly to ARIA-H pathogenesis.</p><p><strong>Conclusion: </strong>These findings establish a mechanistic framework for ARIA-H risk and provide concrete molecular predictors to guide antibody engineering strategies. Prioritizing mAbs with controlled amyloid clearance, C-terminal binding domains, and IgG1 frameworks may enhance therapeutic safety, advancing precision immunotherapy for Alzheimer's disease.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014052","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":"Association between Suicidal Ideation and Immune Parameters in Firstepisode Patients with Schizophrenia.","authors":"Yu Xia, Xiaoni Guan, Meihong Xiu, Fengchun Wu","doi":"10.2174/011570159X384619250727094057","DOIUrl":"https://doi.org/10.2174/011570159X384619250727094057","url":null,"abstract":"<p><strong>Introduction: </strong>Disturbed immunity and inflammation have been associated with the pathogenesis of schizophrenia (SZ) and suicidal behaviors. We hypothesized that the neutrophil-tolymphocyte ratio (NLR) was associated with the increased risk of suicide ideation (SI) in patients with SZ.</p><p><strong>Methods: </strong>A total of 97 drug-naïve first-episode patients with SZ (15 with SI and 82 without SI) were recruited in the present study. The symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), and differential white cell counts and SI were assessed for all patients.</p><p><strong>Results: </strong>Patients in the SI group had higher NLR values and more severe clinical symptoms than the non-SI group (all p<0.05). Differences remained significant when controlling for smoking, sex, BMI, and age. Logistic regression analysis showed that NLR values were an independent predictor of SI in first-episode patients with SZ after controlling for clinical symptoms, smoking status, marital status, education, sex, body mass index (BMI), and age.</p><p><strong>Discussion: </strong>This study indicates a predictive role of NLR in SI at the first onset of SZ. It also suggests that monitoring NLR could be a useful clinical tool for identifying patients who may be at higher risk for SI, particularly at the onset of the disorder.</p><p><strong>Conclusion: </strong>Our findings add to the understanding of the biological factors that may contribute to SI in SZ.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946060","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":"Mitochondria as a Therapeutic Target in Neurodegeneration: Strategies for Restoring Cellular Homeostasis.","authors":"Bartosz Twarowski, Iwona Piątkowska-Chmiel, Mariola Herbet","doi":"10.2174/011570159X389970250727031306","DOIUrl":"https://doi.org/10.2174/011570159X389970250727031306","url":null,"abstract":"<p><p>Ageing is a complex biological process marked by a gradual decline in bodily functions at the cellular, tissue, and organ levels, resulting from molecular damage and environmental influences. It increases disease risk, particularly in older adults with neurodegenerative conditions characterized by progressive neuronal loss and neurological symptoms such as cognitive and motor impairments. Key mechanisms include abnormal protein accumulation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. Disruption of cellular homeostasis prevents the maintenance of internal conditions such as pH and glucose levels. Mitochondria, known as the cell's \"powerhouses,\" are essential for ATP production, DNA protection, and metabolic regulation, supporting cellular structures. Their dysfunction plays a crucial role in the progression of neurodegenerative diseases. Factors like chronic inflammation, ATP deficiency, excessive production of reactive oxygen species (ROS), and calcium imbalance leads to oxidative stress and neuronal damage, exacerbating neurodegeneration. Current therapies mainly focus on symptom relief, emphasizing the urgent need for new treatment strategies. Given the key role of mitochondrial dysfunction, therapies aiming to restore mitochondrial homeostasis are gaining increasing attention. Mitochondrial antioxidants such as MitoQ, MitoTEMPO, and SkQ1 have shown neuroprotective, anti-inflammatory, and antioxidant properties. Research into their therapeutic potential may lead to the development of effective drugs that restore mitochondrial function and improve quality of life of the patienst.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871815","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":"Inhibition of the P2Y2 Receptor Promotes Facial Nerve Function by Enhancing Neuron Autophagy.","authors":"Xianmin Song, Yingna Gao, Minhui Zhu, Hongliang Zheng, Wei Wang, Shicai Chen","doi":"10.2174/011570159X349328250717113503","DOIUrl":"https://doi.org/10.2174/011570159X349328250717113503","url":null,"abstract":"<p><strong>Objective: </strong>Facial nerve injury induces autophagy and apoptosis in facial nerve nucleus motoneurons of the CNS, impairing nerve regeneration and functional recovery. The function of P2Y2R after facial nerve injury remains to be determined. This study hypothesizes that inhibiting P2Y2R may play a protective role in facial nerve injury by modulating the autophagy signaling pathway.</p><p><strong>Methods: </strong>An in vivo mouse model of facial nerve crush injury was utilized in this study. Mice received either a P2Y2R agonist or antagonist through intrathecal injections of 10 μL/daily for 4 weeks. This study measured facial nerve function, examined fibrogenesis, and analyzed expression of autophagy regulatory proteins. In an in vitro experiment, NSC34 cells were treated with a P2Y2R agonist or an antagonist, and changes in the levels of phosphorylated PI3K, Akt, and mTOR, as well as autophagy regulatory proteins determined.</p><p><strong>Results: </strong>Inhibition of P2Y2R significantly increased autophagy levels and enhanced facial nerve function. These protective outcomes were linked to the suppression of phosphorylated PI3K, Akt, and mTOR signaling pathways.</p><p><strong>Conclusion: </strong>The study suggests that P2Y2R inhibition may improve facial nerve function by improving autophagy, making it a promising therapeutic approach for treating facial nerve injury.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834480","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}