Journal of Molecular Neuroscience最新文献

Glial Cells in Alzheimer's Disease: Pathogenic Mechanisms and Therapeutic Frontiers. 阿尔茨海默病中的神经胶质细胞：致病机制和治疗前沿。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-07-12 DOI: 10.1007/s12031-025-02379-8

Moumita Sil, Nabanita Mukherjee, Ishita Chatterjee, Ankita Ghosh, Arunava Goswami

{"title":"Glial Cells in Alzheimer's Disease: Pathogenic Mechanisms and Therapeutic Frontiers.","authors":"Moumita Sil, Nabanita Mukherjee, Ishita Chatterjee, Ankita Ghosh, Arunava Goswami","doi":"10.1007/s12031-025-02379-8","DOIUrl":"https://doi.org/10.1007/s12031-025-02379-8","url":null,"abstract":"The rising incidence of brain diseases parallels the global trend of an aging population, with Alzheimer's disease (AD) being a leading neurodegenerative disorder characterized by memory loss, dementia, and cognitive decline. Despite extensive research, current treatments for AD remain largely symptomatic and have had limited success in halting disease progression, thereby shifting attention toward glial cells as promising therapeutic targets due to their emerging roles in AD pathogenesis. Astrocytes are involved in both beneficial and pathological processes in AD, such as cytokine secretion, Aβ removal, metabolic support, and tau pathology, with deficiency resulting in neuroinflammation and excitotoxicity. Microglia have dual functions in AD by phagocytosing amyloid plaques and limiting tau spread in initial phases but may develop a pro-inflammatory, neurodegenerative phenotype with progression of the disease. Oligodendrocytes and their precursors are involved in Aβ generation and myelin homeostasis, and their disturbance is responsible for white matter lesions and cognitive impairment, though their exact mechanisms are less clear. This review also examines emerging therapeutic strategies targeting glial cells, including modulating TREM2 pathways and novel drug candidates. These methods highlight the therapeutic value of the glial cells and provide valuable leads for furthering the treatment of AD by elucidating their changing roles in the course of the disease.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"87"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Decoding EGFR A289 Mutation in Glioblastoma: A Predictive Biomarker Framework and Targeted Therapeutic Insights. 解码胶质母细胞瘤中的EGFR A289突变：预测性生物标志物框架和靶向治疗见解。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-07-12 DOI: 10.1007/s12031-025-02381-0

Xiaoxue Zhu, Haitao Fu, Xuejing Li, Hang Zhou, Zekai Li, Luyang Xie, Guilin Li

{"title":"Decoding EGFR A289 Mutation in Glioblastoma: A Predictive Biomarker Framework and Targeted Therapeutic Insights.","authors":"Xiaoxue Zhu, Haitao Fu, Xuejing Li, Hang Zhou, Zekai Li, Luyang Xie, Guilin Li","doi":"10.1007/s12031-025-02381-0","DOIUrl":"https://doi.org/10.1007/s12031-025-02381-0","url":null,"abstract":"Glioblastoma (GBM) is the most common primary malignant intracranial tumor, accounting for over 50% of central nervous system tumors. Among EGFR mutations in GBM, A289 is a prevalent point mutation associated with poor prognosis, yet its unique characteristics and role in malignant progression remain unclear. To address this, we analyzed EGFR A289 mutation frequency by integrating tumor mutation data from TCGA and CGGA databases as well as Beijing Tiantan Hospital's Neuropathology Center. We established U87-MG cell lines carrying EGFR A289T/V/D mutations via lentiviral transduction and performed transcriptome sequencing. Differential gene expression analysis was assessed by integrating the cell lines' and TCGA tumor tissues' transcriptomic data. Followed by gene correlation analysis, univariate logistic regression, and LASSO regression, the key differential expressed genes were identified, leading to the development of a multivariable logistic regression model to decode the EGFR A289 mutation. Our study identified EGFR A289 as the most frequent EGFR missense mutation in GBM. The prediction model and nomogram, based on EGFR, CLEC18B, and PDK1 expression, exhibited strong predictive performance. Additionally, drug sensitivity analysis and in vitro validation demonstrated that gefitinib and XAV939 hold therapeutic potential for GBM with EGFR A289 mutations, showing significant synergistic effects. These findings provide critical insights into the role of EGFR A289 mutation in GBM, enabling precise diagnosis and offering targeted therapeutic strategies to overcome chemoresistance.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"88"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Non-targeted and Targeted Metabolomics Techniques Reveal Striatal Metabolome Characteristics in the Ketamine-Induced Conditioned Place Preference Mice Model. 非靶向和靶向代谢组学技术揭示氯胺酮诱导条件位置偏好小鼠模型纹状体代谢组学特征。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-07-12 DOI: 10.1007/s12031-025-02382-z

Weihao Fan, Yi Ye, Hongkun Yang, Ying Wei, Kaiting Shi, Xinyu Yang, Jian Li, Zilong Wang, Yiming Sun, Linchuan Liao

{"title":"Non-targeted and Targeted Metabolomics Techniques Reveal Striatal Metabolome Characteristics in the Ketamine-Induced Conditioned Place Preference Mice Model.","authors":"Weihao Fan, Yi Ye, Hongkun Yang, Ying Wei, Kaiting Shi, Xinyu Yang, Jian Li, Zilong Wang, Yiming Sun, Linchuan Liao","doi":"10.1007/s12031-025-02382-z","DOIUrl":"https://doi.org/10.1007/s12031-025-02382-z","url":null,"abstract":"Ketamine is a synthesized anesthetic drug that was used extensively as a surgical anesthetic in the 1960s. Currently, ketamine is being investigated extensively for its potential as a treatment for depression. However, the addictive nature of ketamine has become an issue that cannot be ignored at this stage. As of now, there is no clear understanding of the changes in striatal metabolites and their relative metabolic pathways under the addictive effect of ketamine. In this study, a stable model of ketamine-induced conditioned place preference (CPP) was established. Non-targeted metabolomics and targeted metabolomics techniques, based on the ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-QE/MS) and the UHPLC-MS platform, were employed to uncover the metabolic characteristics and neurotransmitter profiles of the striatum after ketamine abuse in mice. Potential biomarkers and related differential metabolic pathways of this model have been revealed. In non-targeted metabolomics analysis, striatal differential metabolites mainly involve pathways related to arginine synthesis, purine metabolism, and morphine addiction. In targeted metabolism, the striatum of mice receiving ketamine showed an increase in the content of the neurotransmitter kynurenine (Kyn) and a decrease in the content of the neurotransmitter dopamine (DA). Our study suggested that Kyn and DA metabolism disturbances might be associated with ketamine-induced CPP phenotypes and provided a new perspective for investigating the addiction mechanisms of ketamine.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"89"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Vascular Cell Adhesion Molecule-1 and Complement C3 involvement in Febrile Seizures in Children. 血管细胞粘附分子-1和补体C3参与儿童热性惊厥。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-07-09 DOI: 10.1007/s12031-025-02385-w

Sevim Şahin, Elif Şimşek, Serap Özer Yaman, Süleyman Caner Karahan, Mukaddes Kalyoncu

{"title":"Vascular Cell Adhesion Molecule-1 and Complement C3 involvement in Febrile Seizures in Children.","authors":"Sevim Şahin, Elif Şimşek, Serap Özer Yaman, Süleyman Caner Karahan, Mukaddes Kalyoncu","doi":"10.1007/s12031-025-02385-w","DOIUrl":"https://doi.org/10.1007/s12031-025-02385-w","url":null,"abstract":"Elevated inflammation, characterized by increased proinflammatory cytokine levels in febrile seizures (FSs), has been well documented; however, the underlying causes and contributing factors remain unclear. This study aimed to investigate the molecular components that may contribute to or protect against inflammation in children with FS. The study involved children aged 6-60 months with FS (FS group, n = 29), afebrile seizures (AS group, n = 17), and febrile controls (FC group, n = 30). Leukocyte count, C-reactive protein, complement C3 and C4, fibrinogen, intercellular and vascular cell adhesion molecules (ICAM-1, VCAM-1), adrenocorticotropic hormone (ACTH), and cortisol levels were measured at onset (T1) and 24 h later (T2) in the seizure groups and at T1 in the FC group, whose samples served as controls for both periods alongside the AS group. At T2 time compared with T1, VCAM-1 levels increased and C3 levels decreased in the FS group, whereas ICAM-1 levels increased in the AS group (p = 0.001, p = 0.048, p = 0.035, respectively). The FS and AS groups had higher leukocyte counts at T1 than T2 (p < 0.001, p = 0.023, respectively). The FS group had higher cortisol levels than the AS group and higher ACTH levels than the FC group at T1 (p < 0.001, p = 0.037, respectively), but at T2, the FS group had lower ACTH levels than the AS and FC groups (p = 0.037, p = 0.006, respectively). In conclusion, VCAM-1 and C3 alterations observed in FS suggest their involvement in inflammation, possibly related to leukocyte migration. Additionally, a higher ACTH peak after FS may be associated with a more benign profile compared with epilepsy.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"86"},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Impaired Flow: Glymphatic Dysfunction in Ischemic Stroke and the Influence of Sex. 血流受损：缺血性脑卒中的淋巴功能障碍及性别的影响。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-07-04 DOI: 10.1007/s12031-025-02377-w

Khiany Mathias, Maiara de Aguiar da Costa, Victoria Linden de Rezende, Victor Duílio Antunes Maragno, Carlos Miguel Klima Felipe, Leyce da Rosa Dos Reis, Cinara Ludvig Gonçalves, Fabricia Petronilho

{"title":"Impaired Flow: Glymphatic Dysfunction in Ischemic Stroke and the Influence of Sex.","authors":"Khiany Mathias, Maiara de Aguiar da Costa, Victoria Linden de Rezende, Victor Duílio Antunes Maragno, Carlos Miguel Klima Felipe, Leyce da Rosa Dos Reis, Cinara Ludvig Gonçalves, Fabricia Petronilho","doi":"10.1007/s12031-025-02377-w","DOIUrl":"https://doi.org/10.1007/s12031-025-02377-w","url":null,"abstract":"The glymphatic system, essential for the clearance of metabolic waste from the brain, plays a complex role in the context of ischemic stroke (IS), influencing both the acute phase and long-term recovery. Following IS, impairment in cerebrospinal fluid (CSF) flow and in the clearance of neurotoxic substances, such as beta-amyloid and tau proteins, is observed. This dysfunction contributes to the accumulation of waste products in the brain parenchyma, increasing the risk of complications such as post-stroke dementia and depression. Several mechanisms are involved in this process, including perivascular space dilation, changes in aquaporin-4 expression and polarization, and the presence of reactive astrogliosis, all of which further compromise glymphatic function. These factors are also directly associated with the development of cerebral edema, a critical complication that exacerbates the severity of IS. Moreover, growing evidence suggests that biological sex may influence the glymphatic system's response to IS. Studies indicate that women may exhibit a more efficient glymphatic response, potentially mediated by hormones such as estrogen, which could offer greater protection against the deleterious effects of cerebral ischemia. However, further research is needed to confirm this hypothesis and to better understand the mechanisms underlying this sex-based difference. This review article aims to compile and critically discuss current evidence regarding the role of the glymphatic system in IS pathophysiology, also highlighting potential sex-related differences and their implications for future therapeutic approaches.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"85"},"PeriodicalIF":2.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation. 非西汀通过nrf2介导的自噬激活减弱肌萎缩性侧索硬化症中SOD1突变体的聚集。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-28 DOI: 10.1007/s12031-025-02376-x

Tianhang Wang, Ying Wang, Yueqing Yang, Shuyu Wang, Xudong Wang, Honglin Feng

{"title":"Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation.","authors":"Tianhang Wang, Ying Wang, Yueqing Yang, Shuyu Wang, Xudong Wang, Honglin Feng","doi":"10.1007/s12031-025-02376-x","DOIUrl":"https://doi.org/10.1007/s12031-025-02376-x","url":null,"abstract":"Dysregulated autophagy and copper/zinc superoxide dismutase (SOD1) protein aggregation play a crucial role in amyotrophic lateral sclerosis (ALS). Here, we used stably transfected NSC34 motor neuron-like cells: (1) SOD1G93A mutants (G93A), (2) wild-type SOD1 (WT) controls, and (3) empty vector (EV) controls to observe the effects of fisetin. Pharmacological autophagy inhibition (Bafilomycin A1, 40 nM) and nuclear factor erythroid 2-related factor 2 (Nrf2) gene silencing (siRNA transfection) were employed to dissect molecular pathways. Protein aggregation dynamics and autophagy markers (LC3, p62/SQSTM1) were quantified through immunofluorescence and immunoblotting. SOD1G93A models exhibited impaired autophagic flux evidenced by elevated LC3-II and p62 levels, correlating with increased detergent-insoluble SOD1 aggregates. Fisetin treatment (1-10 μ M) dose-dependently reduced both soluble and aggregated SOD1G93A protein, concomitantly with restored autophagic flux. Mechanistically, fisetin promoted nuclear translocation while decreasing cytoplasmic Nrf2. After administration of an autophagy inhibitor and interference with Nrf2, the regulation of fisetin on p62 and mutant hSOD1 protein was inhibited. Our findings demonstrate that fisetin ameliorates mutant SOD1 proteotoxicity through coordinated activation of Nrf2-mediated autophagy pathways, suggesting therapeutic potential for SOD1-associated ALS pathologies.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"84"},"PeriodicalIF":2.8,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

3-Phenoxybenzoic Acid Induces Neuronal Pentraxin 2 to Upregulate Complement Activity and Promotes Microglia-Mediated Neuronal Synaptic Damage. 3-苯氧苯甲酸诱导神经元戊烷素2上调补体活性并促进小胶质细胞介导的神经元突触损伤。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-26 DOI: 10.1007/s12031-025-02374-z

Guiling Hu, Kaidong Wang, Chenyang Wu, Qi Liu, Qianrong Zhang, Ai Qi, Min Huang

{"title":"3-Phenoxybenzoic Acid Induces Neuronal Pentraxin 2 to Upregulate Complement Activity and Promotes Microglia-Mediated Neuronal Synaptic Damage.","authors":"Guiling Hu, Kaidong Wang, Chenyang Wu, Qi Liu, Qianrong Zhang, Ai Qi, Min Huang","doi":"10.1007/s12031-025-02374-z","DOIUrl":"https://doi.org/10.1007/s12031-025-02374-z","url":null,"abstract":"3-Phenoxybenzoic acid (3-PBA) has been demonstrated to be associated with neurrotoxicity, however, the precise mechanism through which it exerts its neurotoxic effects remains to be fully elucidated. In this study, an investigation was conducted into the neuroimmunotoxicity of 3-PBA from an immunological perspective, with a combination of traditional toxicological methods and computer simulations being utilized in the research process. In vivo, 3-PBA has been shown to cause microstructural damage to early synapses in the mouse brain, which is widely accepted as the primary cause of cognitive dysfunction in mice. In vivo, it has been demonstrated that synaptic damage is induced by the upregulation of complement activity by neuronal pentraxin 2 (NP2), which in turn promotes microglia-mediated synaptic damage. Moreover, molecular docking simulations confirmed the interaction between 3-PBA and NP2. The present findings extend from a neurotoxicity perspective to 3-PBA-associated computer simulations, highlighting NP2 as a molecular initiating protein for 3-PBA-induced neurotoxicity. Additionally, the heightened complement activity downstream facilitated synaptic harm by microglia, causing a decrease in synaptic density and ensuing cognitive impairment. The outcomes of this study expand our knowledge of the neurotoxic nature of 3-PBA and supply hints and a theoretical foundation for evaluating its risks.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"83"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Editorial: Scientists Should Be the Buffer of Turmoil. 社论：科学家应该成为动荡的缓冲器。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-23 DOI: 10.1007/s12031-025-02375-y

Noam Shomron

引用次数: 0

The Progress of Cognitive Dysfunction Impairment Caused by Temporal Lobe Epilepsy. 颞叶癫痫所致认知功能障碍的研究进展。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-21 DOI: 10.1007/s12031-025-02365-0

Qianqian Wang, Yanguang Geng, Xin Li, Yunhua Hao, Shuqi Huang

{"title":"The Progress of Cognitive Dysfunction Impairment Caused by Temporal Lobe Epilepsy.","authors":"Qianqian Wang, Yanguang Geng, Xin Li, Yunhua Hao, Shuqi Huang","doi":"10.1007/s12031-025-02365-0","DOIUrl":"10.1007/s12031-025-02365-0","url":null,"abstract":"Epilepsy is a chronic disease that is characterized primarily by seizures. One of the most common and detrimental comorbidities of epilepsy is cognitive impairment. Approximately, 30-40% of patients with chronic epilepsy experience cognitive impairment, which significantly impacts their daily functioning and quality of life and imposes a heavy burden on both patients and society. Numerous studies have established a correlation between epilepsy and cognitive impairment, showing that epilepsy patients exhibit varying degrees of cognitive deficits influenced by various factors. However, the clinical manifestations, underlying mechanisms, and influencing factors of cognitive impairment in epilepsy patients are still not fully understood. In this review, we aim to summarize and integrate the current understanding of the mechanisms underlying learning and memory impairments in temporal lobe epilepsy (TLE). We summarize the effects of abnormal neuronal discharges, synaptic plasticity alterations, neuroinflammation, and other potential contributors to cognitive dysfunction in TLE.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"81"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use? 在发现PACAP的神经保护作用30多年后，是什么阻碍了它的临床应用？

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-21 DOI: 10.1007/s12031-025-02366-z

Asma Cherait, Xavier Xifró, Dora Reglodi, David Vaudry

{"title":"More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?","authors":"Asma Cherait, Xavier Xifró, Dora Reglodi, David Vaudry","doi":"10.1007/s12031-025-02366-z","DOIUrl":"10.1007/s12031-025-02366-z","url":null,"abstract":"Discovered in 1989, pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with strong neuroprotective properties, as shown in various neurodegenerative preclinical models of Parkinson, Alzheimer, or Huntington diseases. PACAP neuroprotection has also been reported in animal models of cerebral ischemia and traumatic brain injury. The neuroprotective effect of PACAP occurs through its capacity to modulate most of the multiphasic aspects of neuronal diseases, such as oxidative stress, neuronal cell death, and inflammation. However, more than three decades after its discovery, and although PACAP neurotrophic and neuroprotective activities have now been largely documented, its clinical use is still awaited. Thus, the aim of this manuscript is to discuss the main reasons which limit the use of PACAP as a therapeutic agent for the treatment of neuronal diseases. To achieve this objective, an opinion survey has been conducted among experts in the field of PACAP, and a bibliographic investigation was carried out.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"80"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0