Neurochemical Research最新文献

{"title":"Microglia-Derived Exosomal miR-223-3p Targets the RhoB-NF-κB-CCL11 Axis in Astrocytes and Relieves Neuronal Damage in Subarachnoid Hemorrhage","authors":"Fanmeng Zeng,&nbsp;Zhirui Liao,&nbsp;Lei Li,&nbsp;Bo Yang,&nbsp;Jinshui Lin","doi":"10.1007/s11064-025-04566-w","DOIUrl":"10.1007/s11064-025-04566-w","url":null,"abstract":"<div><p>Neuroinflammation mediated by reactive microglia and astrocytes is the primary pathological process of early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study aimed to investigate the role of microglia-derived exosomes in astrocytic activation and neuronal damage in SAH. An SAH mouse model was generated via endovascular perforation. Following the administration of miR-223-3p-enriched microglia-derived exosomes or a CCL11 antibody (anti-CCL11), the neurological functions of mice were evaluated. Nissl staining and TUNEL staining were carried out to assess neuronal apoptosis. The activation of microglia and astrocytes was examined by immunofluorescence. Hemin-treated primary cultured microglia and astrocytes were then cocultured with miR-223-3p-enriched exosomes or anti-CCL11. Furthermore, the conditioned medium of the cells was collected and added to HT22 cells. The viability, ROS level, and degree of oxidative stress in HT22 cells were determined. The mechanism of miR-223-3p to target RhoB was verified via a dual-luciferase reporter gene assay. Reduced miR-223-3p expression was detected in SAH mice, whereas CCL11 and inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-18) were elevated. Microglia-derived exosomal miR-223-3p or anti-CCL11 significantly mitigated neurological deficits and neuronal damage, and relieved microglial and astrocytic activation in the SAH model. In vitro experiments revealed that hemin induced significant activation of microglia and astrocytes. MiR-223-3p-enriched exosomes or anti-CCL11 attenuated hemin-induced microglial and astrocytic activation and attenuated HT22 cell damage through the inhibition of ROS and oxidative stress. Mechanistic studies revealed that miR-223-3p targeted RhoB and inhibited the RhoB/NF-κB/CCL11 axis in astrocytes. Microglia-derived exosomal miR-223-3p relieves EBI after SAH through the inhibition of astrocytic activation via the RhoB-NF-κB-CCL11 pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"d-Serine’s Journey Between Stars and Synapses","authors":"Sarah Mountadem,&nbsp;Stéphane Henri Richard Oliet,&nbsp;Aude Panatier","doi":"10.1007/s11064-025-04564-y","DOIUrl":"10.1007/s11064-025-04564-y","url":null,"abstract":"<div><p>Astrocytes play a pivotal role in regulating synaptic transmission, with <span>d</span>-serine emerging as a key gliotransmitter shaping NMDA receptor-dependent functions. This review is focusing on the multifaceted role of astrocytic <span>d</span>-serine from synaptic transmission to cognitive processes. While this review includes the work of other groups, it is mainly based on the findings obtained in our laboratory. Drawing from two decades of research spanning from the hypothalamus to the hippocampus, we here highlight how astrocyte-derived <span>d</span>-serine regulates NMDAR activity, long-term synaptic plasticity, and associated memory. Our findings have revealed the dynamic control exerted by astrocytic processes onto <span>d</span>-serine availability within the synaptic cleft, including the impact of the astrocytic morphological plasticity, the key role played by intracellular Ca²⁺ as well as the involvement of CB1 and EphB3 receptors. We also discuss how an impairment in astrocytic <span>d</span>-serine synthesis can affect the co-agonist availability and consequently impact cognitive functions in neurodegenerative disorders such as Alzheimer’s Disease. To conclude, this review highlights the role of astrocytic <span>d</span>-serine in astrocyte-neuron communication and higher-order brain functions.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12521327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraorbital Electroacupuncture Promotes Oculomotor Nerve Repair by Inducing M2 Macrophage Polarization via the JAK1/STAT6 Pathway","authors":"Yuan Li,&nbsp;Yi-fei Fan,&nbsp;Xiao-lu Jin,&nbsp;Bing-bing He,&nbsp;Yu-fei Liu,&nbsp;Tong-yan Liu,&nbsp;Ling-yun Zhou","doi":"10.1007/s11064-025-04517-5","DOIUrl":"10.1007/s11064-025-04517-5","url":null,"abstract":"<div><p>Oculomotor nerve injury impairs eye movement and pupil control. Intraorbital electroacupuncture (IEA) is a promising treatment, but its mechanisms remain unclear. This study investigates whether IEA promotes nerve recovery by inducing M2 macrophage polarization through the JAK1/STAT6 pathway. Sprague–Dawley (SD) rats with oculomotor nerve injury were divided into four groups: sham, control, IEA, and IEA + AS1517499 (JAK1/STAT6 inhibitor). Pupil diameter and abduction deviation were measured. Nerve structure was assessed with Luxol fast blue and Nissl staining. Western blotting analyzed JAK1/STAT6 pathway activation, and immunofluorescence quantified M1/M2 macrophages. The IEA group showed significant functional recovery in the oculomotor nerve, as evidenced by improvements in pupil diameter and abduction deviation compared to the control group. Histological analysis revealed better preservation of nerve structure in the IEA group, with reduced signs of damage. Western blot results demonstrated increased phosphorylation of STAT6 in the IEA group, indicating activation of the JAK1/STAT6 pathway. Immunofluorescence double staining revealed a higher ratio of M2 (CD206+, CD163+) macrophages relative to M1(CD86+ , iNOS+) macrophages in the IEA group. This effect was diminished in the IEA + AS1517499 group, suggesting that the therapeutic benefits of IEA are mediated through the JAK1/STAT6 pathway and M2 macrophage polarization. IEA promotes oculomotor nerve repair by inducing M2 macrophage polarization via the JAK1/STAT6 pathway, offering a potential therapeutic strategy for nerve injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Methylsulfonylmethane Mitigates Neurobehavioral Impairment, Oxidative Stress, Changes in Trace Elements and Clock Expression in Alcohol and Circadian-Disrupted C57BL/6J Mice Brain","authors":"Indrani Paramasivan Latha Laxmi,&nbsp;Ramasamy Tamizhselvi","doi":"10.1007/s11064-025-04580-y","DOIUrl":"10.1007/s11064-025-04580-y","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Para-Aminosalicylic Acid Inhibits Manganese-Iron Co-exposure-induced Inflammation via the NF-κB Pathway in Rat Substantia Nigra","authors":"Zhao-cong Li,&nbsp;Yi-fei Wei,&nbsp;Ting-ting Zhou,&nbsp;Thanh-Tung Ho,&nbsp;Jing-jing Luo,&nbsp;Xiao-feng Li,&nbsp;Michael Aschner,&nbsp;Dong-jie Peng,&nbsp;Yue-ming Jiang","doi":"10.1007/s11064-025-04574-w","DOIUrl":"10.1007/s11064-025-04574-w","url":null,"abstract":"<div><p>Manganese (Mn) and iron (Fe) serve as essential cofactors for numerous enzymes and play critical roles in neural functions within the central nervous system. However, chronic overexposure to these metals can disrupt neurophysiological homeostasis. The mechanisms underlying combined Mn–Fe exposure induced neurotoxicity remain unclear. Sodium para-aminosalicylate (PAS-Na), a non-steroidal anti-inflammatory drug capable of crossing the blood-brain barrier, has demonstrated efficacy in treating Mn poisoning. This study investigated the neurotoxic effects of Mn–Fe co-exposure in rats and evaluated the protective role of PAS-Na. Our findings reveal that Mn–Fe co-exposure induced significant weight gain suppression, increased liver coefficient, and extensive motor dysfunction manifested as coordination deficits, balance disturbance, and reduced muscle endurance. Histopathological analysis demonstrated severe neurodegeneration in the substantia nigra, characterized by neuronal atrophy, Nissl body depletion, and dopaminergic neuron loss (evidenced by reduced TH⁺ cells and TH protein expression). Furthermore, co-exposure disrupted metal homeostasis, elevating nigral Fe and Ca levels, and activating the NF-κB pathway, upregulating pro-inflammatory cytokines (IL-1β, TNF-α, IL-6). Notably, PAS-Na treatment (160–240 mg/kg) dose-dependently attenuated these effects through two mechanisms: (1) modulating metal accumulation (particularly Fe) and (2) suppressing NF-κB-mediated neuroinflammation, with preferential inhibition of TNF-α. These findings highlight PAS-Na’s potential as a preventive therapy for metal-induced neurodegeneration, particularly in occupational co-exposure scenarios. The study provides novel insights into synergistic Mn–Fe neurotoxicity and identifies NF-κB inhibition as a promising therapeutic target.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLRs/PI3K/AKT1B Signaling Pathway Is Involved in Modulation of Neuroinflammation in the Rat Hippocampus by Alpha-pinene in Morphine-dependent and Withdrawing Rats","authors":"Shamseddin Ahmadi,&nbsp;Hawsar Rashid Ahmed,&nbsp;Bestan Yousif Abdullah,&nbsp;Shnya Dlshad Taeeb,&nbsp;Mohammad Majidi","doi":"10.1007/s11064-025-04573-x","DOIUrl":"10.1007/s11064-025-04573-x","url":null,"abstract":"<div><p>Toll-like receptors (TLRs) in the brain significantly contribute to various central nervous system (CNS) disorders, including addiction. Morphine’s interaction with TLR4 contributes to dependence and withdrawal. Alpha-pinene, a monoterpene with anti-inflammatory properties, has not been studied for its effects on TLR signaling in morphine dependence and withdrawal. This study investigated alpha-pinene’s impact on hippocampal TLR pathways in morphine-dependent and withdrawing rats. Male Wistar rats were divided into two categories: dependence and withdrawal. The three dependence groups received saline + dimethyl sulfoxide 5% (DMSO), morphine (10 mg/kg) + DMSO, or morphine + alpha-pinene (20 mg/kg) for 10 days. The three withdrawal groups received the same saline or morphine treatments as the dependent groups for ten days. Following this, they went through a 30-day morphine washout phase with daily DMSO (the first and second groups) or alpha-pinene (the third group) administration. Rats in all groups were sacrificed either on day 10 (after repeated injections) or 30 days post-withdrawal. Hippocampal tissues were then dissected and analyzed via Western blot and ELISA to assess protein level changes. Results showed increased hippocampal expression of TLR2, TLR4, TLR10, and MyD88 following morphine dependence and withdrawal, while levels of PI3K, p-AKT1B, and IL-1Ra decreased. Alpha-pinene treatment, whether administered during the 10-days dependence induction period or the 30-days withdrawal period, partially restored these alterations in the TLR pathway. These findings suggest alpha-pinene modulates central immune responses by regulating TLR signaling. This highlights therapeutic potential of alpha-pinene for controlling neuroinflammation and subsequent morphine-related complications like tolerance, addiction, and withdrawal.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Induced Overexpression of Connexin43 in Astrocytes Attenuates the Progression of Experimental Temporal Lobe Epilepsy","authors":"Oussama Kherbouche,&nbsp;Lukas Henning,&nbsp;Pia Niemann,&nbsp;Caroline Geisen,&nbsp;Gerald Seifert,&nbsp;Christian Henneberger,&nbsp;Bernd K. Fleischmann,&nbsp;Christian Steinhäuser,&nbsp;Peter Bedner","doi":"10.1007/s11064-025-04572-y","DOIUrl":"10.1007/s11064-025-04572-y","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04572-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Stress Disrupts Immune and Endocrine Axis, Inducing Persistent Behavioral Impairments in Male Rats: In Silico and In Vivo Insights","authors":"Maryam Saeidi,&nbsp;Gholamreza Hassanzadeh,&nbsp;Fatemeh Rouhollah,&nbsp;Tahmineh Mokhtari","doi":"10.1007/s11064-025-04579-5","DOIUrl":"10.1007/s11064-025-04579-5","url":null,"abstract":"<div><p>Chronic stress disrupts immune-endocrine balance and contributes to major depressive disorder (MDD) through dysregulated autophagy and neuroinflammation pathways, yet their interactions and persistence remain unclear. This study investigated these mechanisms using chronic restraint stress (CRS) in male Wistar rats and in silico MDD gene analysis. Rats were exposed to CRS for 15 days (Res15) or 30 days (Res30), followed by a 30-day stress-free recovery period without intervention (Res30/Rec30). Behavioral assessments (anxiety, depression-like behaviors, and cognition) were conducted via standard tests. Blood samples were analyzed for neutrophil-to-lymphocyte ratio (NLR) and corticosterone levels. Hippocampal cytokine expression (TNF-α, IL-1β, IL-16), Beclin1 levels, and neuronal damage were evaluated via molecular and histopathological methods. In silico analysis linked these pathways to human MDD by identifying upregulated autophagy- and inflammation-related genes (including IL1B, PTGS2, GNAI3, RAB1A, MAP1LC3B, SQSTM1, and KIF5B), bridging rodent stress models to clinical depression. CRS induced anxiety- and depression-like behaviors, cognitive impairment, hippocampal neurodegeneration, elevated corticosterone and NLR, and upregulation of pro-inflammatory and autophagy markers. Although partial recovery in depression-like behaviors and cytokine levels was observed after 30 days, anxiety-like behaviors, cognitive impairment, elevated NLR, and hippocampal neurodegeneration persisted. These findings reveal persistent neurobiological consequences of chronic stress, advancing understanding of MDD pathophysiology and suggesting that targeting autophagy and neuroinflammation could offer novel treatments for depression, particularly for symptoms that endure post-stress.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioprotective Effects of Ilex paraguariensis Standardized Extract Through Nrf2 Activation and NF-κB Suppression in lipopolysaccharide-treated Astrocytes","authors":"Vanize Mackedanz Ludtke,&nbsp;Thais Marini da Rosa,&nbsp;Natália Pontes Bona,&nbsp;Luana Ferreira Viana dos Reis,&nbsp;Lucas Petitemberte de Souza,&nbsp;William Borges Domingues,&nbsp;Vinicius Farias Campos,&nbsp;Rejane Giacomelli Tavares,&nbsp;Roselia Maria Spanevello,&nbsp;Ingrid Vicente Farias,&nbsp;Nathalia Stark Pedra,&nbsp;Flavio Henrique Reginatto,&nbsp;Francieli Moro Stefanello","doi":"10.1007/s11064-025-04568-8","DOIUrl":"10.1007/s11064-025-04568-8","url":null,"abstract":"<div><p><i>Ilex paraguariensis</i> (IP) is a plant native to South America, traditionally consumed as a beverage and holding significant economic and social value. This plant has been associated with a range of pharmacological activities, including anti-inflammatory and antioxidant effects. Although some studies have suggested its neuroprotective properties, the effects of IP on glial cells, particularly astrocytes, remain poorly understood. Astrocytes play a crucial role in the neuroinflammatory response, and dysfunction in these cells can contribute to the development of neurodegenerative diseases. This study aimed to investigate the glioprotective mechanisms of a standardized IP extract against inflammatory and oxidative damage induced by lipopolysaccharide (LPS) in primary astrocyte cultures. Astrocytes were treated with IP extract (10, 30, 100, and 300 µg/mL) for 24 h, followed by a 3-hour exposure to LPS (1 µg/mL). LPS exposure resulted in the up-regulation of mRNA expression of <i>interleukin-1β</i> and <i>nuclear factor-kappa B</i> genes, increased cell proliferation, and acetylcholinesterase activity, elevated levels of reactive oxygen and nitrogen species, and reduced astrocytic viability, Na⁺, K⁺-ATPase activity, and antioxidant defenses. Treatment with IP extract was able to prevent these effects by reducing pro-inflammatory and oxidative mediators, modulating acetylcholinesterase and Na⁺, K⁺-ATPase activity, enhancing antioxidant defenses, and up-regulating mRNA expression of <i>superoxide dismutase 2</i>, <i>glutathione peroxidase</i>, and <i>nuclear factor erythroid-derived 2-like 2</i> genes. To the best of our knowledge, this is the first study to demonstrate the glioprotective effects of IP extract on astroglial cells, laying the groundwork for future research into the neuroprotective mechanisms of IP related to neuroinflammation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of EDC-Induced Alzheimer’s Disease and of Traditional Chinese Medicine Active Substances in Treating AD and Antagonizing EDC-Induced Effects","authors":"Tong Yang","doi":"10.1007/s11064-025-04570-0","DOIUrl":"10.1007/s11064-025-04570-0","url":null,"abstract":"<div><p>AD, a progressive neurodegenerative disorder, imposes an increasingly heavy burden on global public health, with its pathogenesis remaining incompletely understood. Meanwhile, EDCs—widely present in the environment, food, and consumer products—have emerged as a significant public health concern due to their diverse health risks, including potential contributions to neurodegenerative processes such as AD by disrupting neurohomeostasis. Furthermore, as natural compounds, ginsenosides and other AS have been the focus of numerous studies exploring their role in treating AD, thanks to their advantages of multi-target properties and low side effects. However, the specific molecular pathways through which EDCs induce AD, as well as the mechanisms by which AS may counteract EDC-induced toxicity and intervene in AD, remain unclear. Against this background, this study sought to: (1) explore the molecular pathways through which EDCs may induce AD by disrupting neurohomeostasis; (2) preliminarily investigate the potential of AS in treating AD and antagonizing EDC-induced AD at the molecular level. To achieve these goals, we integrated network toxicology, network pharmacology, and molecular docking to construct a multi-dimensional interaction network among EDCs, AD, and AS. By establishing intersecting target sets for EDCs-AD and AS-AD, core targets were identified via topology analysis of protein-protein interaction (PPI) networks. GO and KEGG enrichment analyses highlighted key pathways, including serotonergic synapse and neuroactive ligand-receptor interaction. Molecular docking further explored interactions between EDCs/AS and core target proteins. The results suggest that EDCs may drive neurodegeneration in AD by impairing synaptic function, while AS may counteract these effects by enhancing synaptic activity, stabilizing membrane microenvironments, inhibiting Aβ aggregation, alleviating neuroinflammation, and restoring metabolic homeostasis. Further analysis indicated that AS exhibit stronger binding ability to core targets compared to EDCs, implying a potential antagonistic effect of AS against EDCs. This study provides insights into the molecular mechanisms underlying EDC-induced AD and establishes a multi-target theoretical framework for AS-mediated antagonism of EDC toxicity, offering a reference for the prevention and treatment of neurodegenerative diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}