CNS & neurological disorders drug targets最新文献

{"title":"Cognitive Decline in Atherosclerotic Diseases: Mechanisms and Potential Solutions.","authors":"Japleen Kaur, Ram Agrawal, Chidurala Rahul, Shreya R Kethiri, Kritika Pathak, Neil Patel, Yashendra Sethi, Nirja Kaka, Mohammad Amjad Kamal","doi":"10.2174/0118715273407961260429052113","DOIUrl":"10.2174/0118715273407961260429052113","url":null,"abstract":"<p><p>Atherosclerosis has been increasingly recognized as a contributor to cognitive decline through mechanisms such as cerebral hypoperfusion, oxidative stress, and chronic inflammation. These mechanisms include cerebral hypoperfusion, which limits oxygen and nutrient supply to the brain; microvascular damage, which impairs small vessel function and blood-brain barrier integrity; chronic inflammation, which promotes neurodegeneration through sustained immune activation; and oxidative stress, which accelerates neuronal aging via mitochondrial dysfunction. This narrative review synthesizes findings from epidemiological studies, mechanistic research, and clinical trials to examine the interplay between atherosclerotic diseases and cognitive impairment. Shared risk factors, including hypertension, diabetes, hyperlipidemia, and smoking, accelerate neurovascular dysfunction and increase susceptibility to dementia. Advances in neuroimaging and biomarker research offer improved diagnostic precision, facilitating early detection and intervention. Preventive strategies, including lifestyle modifications, pharmacological therapies such as statins and antihypertensives, and cognitive rehabilitation, have the potential to mitigate cognitive deterioration associated with atherosclerosis. Despite accumulating evidence, vascular contributions to dementia remain underdiagnosed in clinical settings, highlighting the need for a multidisciplinary approach that integrates cardiovascular and neurological care. A comprehensive strategy encompassing risk stratification, early therapeutic intervention, and long-term monitoring is essential for improving cognitive outcomes in at-risk populations. Future research should focus on refining diagnostic methodologies, optimizing prevention and treatment protocols, and identifying high-risk individuals for targeted interventions. Given the rising global burden of both cardiovascular disease and dementia, a proactive approach addressing modifiable risk factors is critical to reducing morbidity and enhancing quality of life.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-Profiling and Re-purposing of FDA-Approved AntiViral Agents Against Neurological Targets of Memory and Cognition: Molecular Docking and Simulation Approach.","authors":"Mujeeb Ul Naeem, Yousaf Khan, Renato Araújo da Costa, Salma Saeed Khan, Muhammad Faheem","doi":"10.2174/0118715273422165260215182925","DOIUrl":"https://doi.org/10.2174/0118715273422165260215182925","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dementia is a prevalent symptom of Alzheimer's Disease (AD), associated with either low levels of acetylcholine or destruction by enzymes. Such enzymes are acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE). The current research worked on re-purposing of 69 Food and Drug Administration Authority (FDA) approved antiviral agents against targets of AD, including AChE (PDB ID: 4BDT) and BuChE (PDB ID: 5LKT).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Targets proteins like AChE (PDB ID: 4BDT) and BuChE (PDB ID: 5LKT), and their PDB IDs were retrieved from the Protein Data Bank (PDB), purified through Discovery Studio Visualizer 2016 (DSV-2016), and saved in PDB format. Data of 69 FDA-approved antiviral agents and standard donepezil were obtained from different published literature, and structures were downloaded from the PubChem structure search tool. DSV-2016 was used for the purification of the targets. PyRx was utilized for the docking of 69 test agents and the standard drug donepezil. DSV-2016 was used for post-docking analysis. In addition, Physio-chemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry analysis of three potential compounds (based on binding affinity) and molecular dynamic simulation (MDS) were performed using SWISSADME and AMBER24 software, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Docking revealed the binding affinities of Saquinavir (-9.1 kcal.mol-1 ), paritaprevir (-10.8 kcal.mol-1 ), and simeprevir (-10.1 kcal.mol-1 ) with AChE. The recorded binding affinities against BuChE were Saquinavir (-11.7 kcal.mol-1 ), paritaprevir -11.2 kcal.mol-1 ), and simeprevir (-11.4 kcal.mol-1 ). Saquinavir and paritaprevir constructed one hydrogen bond with Threonine (THR38) and Glycine (GLN291), respectively. Simeprevir with Asparagine (ASN283), Valine (VAL282), and Tyrosine (TYR72), granting three hydrogen bonds. The data on lipophilicity was determined in terms of Log Po/w (ILOGP). Water solubility of Saquinavir, Paritaprevir, and Simeprevir demonstrated that the Log S (ESOL) value is much higher, and hence the mentioned three compounds are water insoluble. Saquinavir, paritaprevir, and simeprevir were subjected to molecular dynamics simulations, which showed good interactions of the test agents with BuChE compared to AChE.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The study revealed that already approved 69 FDA anti-viral agents showed potential interaction with the selected targets (AChE and BuChE). Three compounds, saquinavir, paritaprevir, and simeprevir, were found with high binding affinities. As they are utilized in human life for various viral infections with known pharmacology and pharmacokinetics data, we can repurpose such a drug to be active against memory loss or cognitive problems.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Based on the applied computational techniques on 69 FDA-approved agents, including molecular docking, SWISS-ADME, and MDS, we identified saquinavir, simeprevir, a","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on Intervention Strategies Targeting the Gut-Brain Axis in Alzheimer`s Disease.","authors":"Boyuan Xia, Shijing Wu, Weihua Yu, Yang Lü","doi":"10.2174/0118715273431295251201140053","DOIUrl":"https://doi.org/10.2174/0118715273431295251201140053","url":null,"abstract":"<p><p>As the most common neurodegenerative disease in the world, Alzheimer's Disease (AD) is characterized by a complex pathogenesis and a lack of effective treatments. In recent years, breakthroughs in the Gut-Brain Axis (GBA) theory have provided a new direction for AD intervention. Studies have shown that AD patients commonly exhibit gut dysbiosis, accompanied by decreased Short-Chain Fatty Acid (SCFA) levels, endotoxin leakage, and increased systemic inflammation, which accelerate cognitive decline via neuroinflammation, Aβ deposition, and synaptic dysfunction. Based on this, intervention strategies targeting the GBA have emerged as a focus of research for slowing down the pathological process of AD. In this study, we systematically summarize the mechanisms linking gut microbiota dysbiosis to AD pathology. This includes the roles of metabolites (e.g., SCFA, LPS, and TMAO) in modulating neuroinflammation and Blood-Brain Barrier (BBB) permeability, as well as the critical involvement of vagal nerve pathways in gut-brain signaling. We further explored the potential of probiotics to improve cognitive function by restoring microbial homeostasis, enhancing anti-inflammatory effects, and elevating neurotrophic factor levels; dietary interventions (e.g., the Mediterranean and MIND diets) to reduce AD risk by modulating microbial composition and metabolic activity; and Fecal Microbiota Transplantation (FMT) to reduce Aβ plaque deposition and mitigate neuroinflammation. Despite promising findings, challenges persist, including discrepancies between animal models and human subjects, individual variability in microbiota composition, and an incomplete understanding of underlying mechanisms. In the future, it will be necessary to combine multiple technologies to develop personalized intervention protocols and optimize clinical translation processes, providing a theoretical basis for the precise treatment of AD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational Design of (Oxadiazol-2-yl) Thiazolidin-4-one Derivatives for Parkinson's Disease: Insights from MD Simulations and Quantum Studies.","authors":"Asif Shaik, Krishna Shevate, Anik Sen, Shanish Antony A, Gomathy Subramanian","doi":"10.2174/0118715273437267251211144051","DOIUrl":"https://doi.org/10.2174/0118715273437267251211144051","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in the substantia nigra. Sirtuin 3 (SIRT3), a mitochondrial NAD⁺-dependent deacetylase, has emerged as a promising therapeutic target due to its vital role in mitochondrial homeostasis and resistance to oxidative stress. However, existing SIRT3 modulators suffer from poor selectivity, suboptimal CNS penetration, and limited binding affinity. This study aimed to design and evaluate novel oxadiazole-thiazolidin-4-one hybrid compounds as potential SIRT3 modulators with improved neuroprotective profiles.</p><p><strong>Methods: </strong>A comprehensive computational workflow was carried out using the Schrödinger Suite 2025-1, including ADMET profiling, molecular docking, molecular dynamics (MD) simulations, Thermal MM/GBSA binding free energy estimation, and protein dynamics analyses (DCCM, PCA, FEL). Additionally, Density Functional Theory (DFT) and Fukui function analyses were conducted to elucidate electronic properties and reactive sites relevant to bioactivity.</p><p><strong>Results: </strong>The designed hybrids exhibited higher SIRT3 binding affinities than known modulators, with binding free energies ranging from -8.9 to -4.88 kcal/mol compared to resveratrol (-7.14 kcal/mol). Among them, TZOX04 [3-(5-benzyl-1,3,4-oxadiazol-2-yl)-2-(2,3,4-trihydroxyphenyl)thiazolidin-4- one] demonstrated the strongest binding energy (-8.94 kcal/mol), favorable drug-likeness, and optimal CNS permeability (logBB = 0.42).</p><p><strong>Discussion: </strong>Molecular dynamics confirmed the stability of the SIRT3-TZOX04 complex over 100 ns, while DFT and Fukui analyses identified key electron-rich regions contributing to reactivity and interaction potential. The oxadiazole-thiazolidinone hybridization approach provided a significant improvement in binding and pharmacokinetic behaviour over existing modulators.</p><p><strong>Conclusion: </strong>This work represents the first systematic investigation of oxadiazole-thiazolidin-4-one hybrids as SIRT3 modulators. TZOX04 emerged as a promising lead compound with enhanced binding affinity, stability, and pharmacokinetic characteristics for PD therapy. These findings warrant future synthetic and biochemical validation to confirm therapeutic efficacy.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Gut-Brain Connection: Exploring the Connection Between the Gastrointestinal System and Parkinson's Disease.","authors":"Ge YuXuan, Muhammad Khalid Iqbal, Bakhtawar Khan, Hamid Khan, Syed Shahab Ud Din Shah, Fawaz Al-Hussain, Mubin Mustafa Kiyani, Shahid Bashir","doi":"10.2174/0118715273419693251206130059","DOIUrl":"https://doi.org/10.2174/0118715273419693251206130059","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by motor and non-motor symptoms. Recent studies indicate that the gut-brain axis contributes to both the initiation and progression of PD, a disorder that primarily affects the central nervous system. This article reviews current research on the interaction between the central nervous system and the gastrointestinal tract in PD. The vagus nerve, areas of the enteric nervous system (ENS), systemic inflammation, and the microbiome are all involved in this interaction. For example, recent studies have shown PD-related effects such as abnormal distribution of gut bacteria, increased gut barrier permeability, and α-synuclein transport from the gut to the brain. A comprehensive evaluation of motor and non-motor symptoms was conducted. Additionally, we explored drugs that specifically target the gastrointestinal system, the possible gastrointestinal symptoms of PD, and how these symptoms may serve as early indicators of the disease. Our article also discusses dietary modifications, probiotics, and fecal microbiota transplantation as potential treatments for PD. By reviewing clinical and basic scientific research as well as translational applications, this article highlights the relationship between the central nervous system and the digestive system in PD. A better understanding of this complex connection may lead to improved detection and treatment of this debilitating disease and offer new opportunities for prevention and therapy. Finally, this paper suggests directions for further research in this area.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetrandrine Attenuates Cerebral Ischemia/Reperfusion Injury by Regulating Th17/Treg Balance and Mediating PI3K/Akt Pathway in Mice, Based on Network Pharmacology Analysis.","authors":"Huanyu Gou, Feng Li, Zishan Huang, Jiarui Zheng, Yuzhen Guo, Mingjiang Yao","doi":"10.2174/0118715273428782260117040032","DOIUrl":"https://doi.org/10.2174/0118715273428782260117040032","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Stroke has found to be the second leading cause of death in China. Research indicates that the immune imbalance of Th17/Treg is an important pathophysiological alteration and the cause of poor prognosis after ischemic stroke, the most common type of stroke. Tetrandrine (Tet), a bisbenzyl isoquinoline alkaloid and potential immunoregulator, has been reported to possess therapeutic effect on ischemic stroke; however, the specific mechanism remains to be clarified. This research aims to explore the molecular mechanisms underlying Tet's effects on cerebral ischemiareperfusion injury (CIRI) through bioinformatics methods and experimental validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using public databases, we predicted potential therapeutic targets of Tet against CIRI. Common targets were then used to build a protein-protein interaction (PPI) network, from which key gene targets were identified. Functional and pathway enrichment analyses were conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Afterwards, molecular docking and experimental validation were performed to confirm the predictions. The middle cerebral artery occlusion and reperfusion (MCAO/R) mice model was established. Twenty-four hours after Tet injection (intraperitoneally, 25 and 50 mg/kg), behavior index evaluation, cerebral blood flow, and tetrazolium chloride (TTC) staining were performed. Pathological changes on cortex, striatum, and hippocampus were observed using hematoxylin-eosin (HE) staining. Percentages of Th17 cells and Treg cells were determined by flow cytometry analysis. The expressions of mRNAs of Th17/Treg markers were measured by quantitative real-time polymerase chain reaction (qPCR). And the expressions of proteins PI3K/Akt Signaling Pathway were measured by Western blot analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our study identified 52 potential therapeutic targets of Tet for CIRI, with 10 key gene targets selected from PPI network analysis. GO and KEGG enrichment analyses indicated that these targets were primarily associated with the PI3K/Akt signaling pathway and Th17 cell differentiation. Molecular docking suggested potential interactions between Tet and Trp53, Cdk4, and Pik3ca. Experimental validation demonstrated that Tet ameliorated neurological deficits and reduced cerebral ischemic damage. Flow cytometry revealed that, compared to the model group, Tet treatment increased Treg cells while decreasing Th17 cells. Additionally, Tet downregulated RORγt and upregulated FoxP3 at the mRNA level. Western blot analysis further confirmed that Tet reduced the p-Akt/Akt and p-PI3K/PI3K protein expression ratios.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Our integrated approach demonstrates that tetrandrine alleviates CIRI by restoring Th17/Treg balance via PI3K/Akt signaling - a mechanism previously unreported for this alkaloid. The downregulation of RORγt and upregulation of FOXP3 confirm Tet's immunomodulatory sp","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vindeburnol Induces Neuroprotection in Rat Traumatic Brain Injury via Adrenergic Receptor Antagonism.","authors":"Mikhail Ivanov, Lyudmila Borets, Elmira Yakupova, Olga Riabova, Alexander Yurin, Denis Silachev, Vadim Makarov","doi":"10.2174/0118715273454662260416105842","DOIUrl":"https://doi.org/10.2174/0118715273454662260416105842","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Traumatic Brain Injury (TBI) causes substantial neurological deficits and remains a major therapeutic challenge. This study aimed to evaluate the neuroprotective properties of Vindeburnol (VIND), a semi-synthetic derivative of vincamine, and to identify its potential molecular targets and optimal dosing regimen for post-traumatic treatment.</p><p><strong>Methods: </strong>Radioligand binding assays were used to determine VIND affinity for 22 CNS receptors, 7 ion channels, and 1 enzyme at a concentration of 10 μM. The in vivo neuroprotective effect was studied in a rat model of TBI induced by controlled cortical impact. VIND was administered intraperitoneally at doses of 10 or 20 mg/kg daily or every other day for 10 days. Neurological recovery was assessed using the beam-walking and limb-placement tests, and brain lesion volume was quantified by MRI on day 14.</p><p><strong>Results: </strong>VIND showed strong inhibition of radioligand binding at α1- and α2-adrenergic receptors (74% and 84.1%, respectively). In vivo, the most pronounced neuroprotective effect was observed at 20 mg/kg every other day, resulting in approximately a twofold reduction in lesion volume (88.7 ± 6.5 mm3 vs 179.4 ± 19.3 mm3 in saline-treated TBI rats, p < 0.001) and a significant improvement in neurological outcomes. The 10 mg/kg dose showed a non-significant trend towards neuroprotection.</p><p><strong>Discussion: </strong>The neuroprotective effect of VIND is likely mediated by the inhibition of excessive adrenergic receptor activation, resulting in improved neuronal survival and functional recovery. These findings highlight adrenergic modulation as a promising therapeutic mechanism for mitigating post-traumatic brain damage.</p><p><strong>Conclusion: </strong>Vindeburnol demonstrated significant neuroprotective efficacy in a rat model of TBI and may represent a promising pharmacological candidate for post-traumatic neuroprotection.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian Randomization Reveals Potential Drug Targets for Multiple Sclerosis Targeting Ferroptosis.","authors":"Tao Wu, Yuze Cao, Lihua Wang, Zhaoxia Wang, Hongjun Hao, Huixue Zhang","doi":"10.2174/0118715273445879260111145647","DOIUrl":"https://doi.org/10.2174/0118715273445879260111145647","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a multifactorial autoimmune condition, and existing medications offer limited efficacy, especially regarding the control of disease progression. Our previous research has suggested a significant role for ferroptosis in the mechanism of MS, making it a promising therapeutic target.</p><p><strong>Methods: </strong>To identify potential treatment targets related to ferroptosis, we conducted Mendelian randomization analysis. We used transcription and proteomic data for 511 ferroptosis-related proteins extracted from 49 tissues in GTEx v8 and deCODE data to derive genetic instruments. We conducted Mendelian randomization based on summary-level data from the International MS Genetics Consortium (47,429 cases and 68,374 controls). Reverse Mendelian randomization, Steiger filtering, Bayesian colocalization, constrained maximum likelihood, and model averaging-based (cML-MA) method, and phenomewide scanning were performed to strengthen findings. Additionally, we explored protein-protein interaction networks to uncover possible links between target proteins and approved MS therapeutics.</p><p><strong>Results: </strong>Under Bonferroni significance (P < 1.52 × 10-4), Mendelian randomization using cisexpression quantitative trait locus instruments revealed nine ferroptosis-related proteins (STAT3, MAPK1, MAPK3, MAP3K11, CISD2, KEAP1, ZEB1, PVT1, PARP1) with significant results in at least one tissue. Bayesian colocalization indicated that four of them (STAT3, PP.H4=0.97; MAPK1, PP.H4=0.95; MAPK3, PP.H4=0.99; ZEB1, PP.H4=0.96) share variation with MS. Under Bonferroni significance (P < 1.11 × 10-3), two proteins also obtained significant proteomic results (STAT3, P = 1.18 × 10-13, MAPK3, P = 3.25 × 10-8). Regional association analysis and phenomewide Scanning suggest a potential involvement of STAT3 in MS. STAT3 and MAPK3 interact with target proteins of current MS drugs, particularly STAT3.</p><p><strong>Discussion: </strong>These findings highlight the causal involvement of ferroptosis pathways in MS pathogenesis, emphasizing STAT3 and MAPK3 as promising therapeutic candidates. This work broadens current understanding of MS biology and suggests new directions for targeted drug development focused on ferroptosis regulation.</p><p><strong>Conclusion: </strong>Our analysis indicates that genetically predicted ferroptosis-related protein levels of STAT3, MAPK1, MAPK3, and ZEB1 are associated with MS risk. Among them, STAT3 and MAPK3 emerge as potential therapeutic candidates, with STAT3 warranting particular clinical investigation.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish (Danio rerio) as a Model for Neurodegenerative Disease Research: Mechanisms, Biomarkers, and Translational Promise.","authors":"Nikhat Khan, Gaurav Doshi","doi":"10.2174/0118715273442688260330060220","DOIUrl":"https://doi.org/10.2174/0118715273442688260330060220","url":null,"abstract":"<p><p>Zebrafish (Danio rerio) have gained prominence as a versatile vertebrate model for studying neurodegenerative disorders due to their genetic similarity to humans, rapid development, transparency, and suitability for high-throughput drug screening. The usefulness of zebrafish in modelling human neurological disorders is supported by the similarity of their brains' anatomical and neurochemical characteristics, including comparable divisions of the forebrain, midbrain, and hindbrain, as well as dopaminergic, serotonergic, glutamatergic, and GABAergic pathways. Zebrafish have been used to successfully model several neurodegenerative diseases, including Alzheimer's disease (via tau phosphorylation and amyloid-beta aggregation), Parkinson's disease (via dopaminergic neuronal loss and alpha-synuclein pathology), Huntington's disease (via polyglutamine-expanded huntingtin), and amyotrophic lateral sclerosis (via mutant SOD1 and TDP- 43 transgenes). They have also been used to study multiple sclerosis, spinocerebellar ataxias, and Rett syndrome, enabling mechanistic exploration and preclinical drug discovery. This review crucially depicts how zebrafish models provide an affordable, morally acceptable, and scalable platform for early-stage neurodegeneration research. These models complement, rather than replace, rodent- and human-derived systems. Additionally, we will review how to bridge the gap between therapeutic screening and basic mechanistic findings, highlighting their increasing significance in the neuroscience research continuum.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of Neutrophil Extracellular Traps in Stroke: Research Trends and Hotspots.","authors":"Kexin Zhong, Biao Tang","doi":"10.2174/0118715273417315251128141230","DOIUrl":"https://doi.org/10.2174/0118715273417315251128141230","url":null,"abstract":"<p><p>Stroke is the second leading cause of death in the world, requiring innovation in therapeutic methods. Neutrophil Extracellular Traps (NETs), networks released by neutrophils, are associated with stroke. This study explores the trends and hotspots of NETs in stroke through bibliometric analysis. The literature on \"NETs in stroke\" was obtained from the Web of Science Core Collection (WoSCC), published from January 1, 2015, to August 31, 2025. This study displays the collaboration of authors, the influence of different journals and references, and the hotspots of keywords, using visualization tools such as Citespace, VOSviewer, Bibliometric, Bibliometrix, and Excel. A total of 370 available studies in the field of \"NETs in stroke\" were selected. The number of publications in this field has been increasing year by year, with China and the United States leading, indicating that the field has attracted widespread attention in these two countries. Institutional collaborations are primarily limited within the country, and international exchanges are necessary to advance research. De Meyer Simon F. and Frontiers in Immunology are the most productive author and journal, while Tobias A. Fuchs and Blood are the most cited author and journal in the field, respectively. Volker Brinkmann's pioneering work, Extracellular Traps Kill Bacteria, is the most cited reference. Through keyword analysis, it was found that studies on \"NETs in stroke\" primarily focused on ischemic stroke and thrombosis, with tissue factor being a key topic and myocardial ischemia emerging as a potential research trend. This study analyzes trends and hotspots of \"NETs in stroke\" visually, providing data support and a theoretical basis for researchers to identify appropriate collaborators and research directions.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147792226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}