Molecular Neurobiology最新文献

{"title":"Dose-Response Effects of Exercise Training on Circulating Brain-Derived Neurotrophic Factor (BDNF): A Systematic Review and Meta-analysis of Randomised Controlled Trials.","authors":"Gang Huang, Liang Tan, Lianghao Zhu, Qinghua Meng, Chunyu Bao, Xuequan Feng","doi":"10.1007/s12035-026-06272-2","DOIUrl":"https://doi.org/10.1007/s12035-026-06272-2","url":null,"abstract":"<p><p>Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity, but circulating BDNF is not a validated surrogate for brain BDNF. We synthesised randomised controlled trials comparing chronic exercise with a non-exercising control. Change-score standardised mean differences (Hedges' g) were pooled using restricted maximum likelihood and Hartung-Knapp inference. The analysis included 48 trials, 56 exercise-versus-control comparisons and 2361 unique participants. Shared control sample sizes were apportioned across comparisons, with trial-cluster robust sensitivity analyses. Exercise increased circulating BDNF on average (g = 0.41, 95% CI 0.25 to 0.57; p < 0.001), with substantial heterogeneity (I² = 67.0%; 95% prediction interval - 0.54 to 1.36). Serum-based comparisons yielded g = 0.27 (95% CI 0.10 to 0.44) and plasma-based comparisons g = 0.69 (0.37 to 1.00); the matrix moderator was significant in the primary analysis (p = 0.017) but not under trial-cluster robust inference (p = 0.065). Population, modality and intervention duration were not significant primary moderators. In the joint dose model (33 comparisons from 29 trials), neither total prescribed exercise volume (β = 0.037 per 1000 min, p = 0.614) nor vigorous versus moderate intensity (β =  - 0.190, p = 0.361) was associated with the BDNF effect. Weekly-volume and quadratic analyses did not establish a dose-response relationship. The overall effect remained positive after restricting sampling to approximately ≥ 24 h after exercise (g = 0.35, 95% CI 0.12 to 0.58). Egger's test indicated small-study effects (p = 0.011). The certainty of evidence was very low. Chronic exercise is associated with an average increase in circulating BDNF, but heterogeneity, methodological limitations and uncertain moderator effects prevent a biomarker-specific exercise prescription or an inference of increased central BDNF. PROSPERO registration: CRD420261448624.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270916","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":"Beyond a Single Mechanism: The iron-ROS-lipid Peroxidation Axis as a Central Driver of Prodromal Parkinson's Disease.","authors":"Peizhu Lyu, Weikun Shen, Yulin Wang, Xia Chen, Shiping Liu, Yu Zhang, Mula A, Xiaoye Jia, Meiwei Zhang, Nan Bu, Shun Wang, Yan Bai","doi":"10.1007/s12035-026-06220-0","DOIUrl":"https://doi.org/10.1007/s12035-026-06220-0","url":null,"abstract":"<p><p>Neurodegeneration in Parkinson's disease (PD) begins subtly many years before motor symptoms appear. The primary pathological processes involve abnormal aggregation and spread of α-synuclein (α-syn), ongoing glial-mediated neuroinflammation, and disrupted brain iron balance. We suggest that a positive feedback loop involving iron-ROS-lipid peroxidation plays a crucial role in connecting these events and propelling the early stages of PD. Iron overload induces lipid peroxidation through the Fenton reaction, generating products like 4-HNE. These byproducts not only modify α-syn structure but also act as signals that trigger the microglial NLRP3 inflammasome. Additionally, pathological α-syn prompts glial cells to release exosomes containing harmful proteins and oxidized lipids, facilitating the spread of ferroptosis stress between cells and brain regions. This mechanism amplifies damage from single neurons to the entire neural network. This comprehensive framework clarifies the intricate interplay among α-syn pathology, neuroinflammation, and iron imbalance in early PD stages, highlighting ferroptosis as a key driver of disease progression.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270854","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":"Spinal Cord Stimulation Attenuates Cognitive Deficits in Chronic Pain in Association with Modulation of the Microglial lnc-PCM1/PCM1/PKC/IFN-γ Signaling Network.","authors":"Qin Li, Deshan Li, Shunxin Liu, Jiang Zou, Hui Pan, Huaiming Wang, Jinjun Shu, Zheng Zou, Pengjiu Feng, Hongwei Zhang, Aimin Zhang","doi":"10.1007/s12035-026-06285-x","DOIUrl":"https://doi.org/10.1007/s12035-026-06285-x","url":null,"abstract":"<p><p>Neuroinflammation plays a pivotal role in chronic pain with cognitive dysfunction (CPCD), a debilitating condition where effective treatments are limited. While spinal cord stimulation (SCS) is an established analgesic therapy, its potential to ameliorate cognitive deficits via central immunomodulation remains largely unexplored. A rat model of CPCD was generated by spared nerve injury (SNI). RNA sequencing was used to identify SCS-regulated long non-coding RNAs (lncRNAs) in the prefrontal cortex (PFC). The functional involvement of the candidate microglial transcript NONRATT012007.2 (hereafter termed lnc-PCM1) was examined using adeno-associated virus (AAV)-mediated manipulation, behavioral testing, molecular assays, and primary-cell conditioned-medium experiments. SCS improved cognitive performance in CPCD rats. lnc-PCM1 was predominantly expressed in microglia and was reduced after SCS. Lower lnc-PCM1 expression was accompanied by increased pericentriolar material 1 (PCM1), reduced protein kinase C (PKC) phosphorylation and IFN-γ abundance, less M1-polarized microglial activation, and lower pro-inflammatory cytokine release. Conditioned medium from manipulated microglia produced corresponding changes in neuronal oxidative stress, mitochondrial membrane potential, apoptosis-related proteins, and synaptic markers. In vivo overexpression of lnc-PCM1 or knockdown of PCM1 partially attenuated the cognitive and neuroinflammatory effects associated with SCS. The findings support an association between the cognitive effects of SCS and modulation of a microglial lnc-PCM1/PCM1/PKC/IFN-γ signaling network in the PFC. Because formal epistasis and IFN-γ neutralization or receptor-blockade experiments were not performed, the directionality and IFN-γ dependence of this network remain to be established.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270943","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":"Evaluating the Impacts of Inflammatory Proteins on the Risk of Alzheimer's Disease.","authors":"Ziyao Zhang, Hongbao Cao, Ancha Baranova, Fuquan Zhang","doi":"10.1007/s12035-026-06292-y","DOIUrl":"https://doi.org/10.1007/s12035-026-06292-y","url":null,"abstract":"<p><p>Accumulating evidence suggests that inflammation contributes to the pathogenesis of Alzheimer's disease (AD). However, the relationship between circulating inflammatory proteins and AD remains incompletely understood. Two-sample Mendelian randomization (MR) was used to assess the associations of 91 circulating inflammatory proteins with AD. The discovery stage protein GWAS included 14,824 participants, and the validation stage analysis used UK Biobank data from 54,219 participants. The AD dataset comprised 85,934 cases and 401,577 controls. The inverse variance weighted (IVW) method was the primary approach, complemented by weighted median, MR-Egger, heterogeneity, and pleiotropy analyses. MR estimates from both stages were subsequently combined by meta-analysis, followed by drug-gene interaction analyses. In the discovery stage, four proteins showed nominal associations with AD: AXIN1 (OR = 1.082, P = 0.026), NGF (OR = 1.061, P = 0.048), CXCL11 (OR = 0.952, P = 0.017), and TNFRSF9 (OR = 0.946, P = 0.048). However, none survived FDR correction (FDR = 0.799). In the validation stage, only TNFRSF9 reached nominal significance (OR = 0.870, P = 0.031), which did not survive FDR correction (FDR = 0.125); AXIN1 showed an opposite direction. Meta-analysis provided suggestive pooled estimates for CXCL11 (OR = 0.956, P = 9.34 × 10⁻³), TNFRSF9 (OR = 0.926, P = 0.034), and NGF (OR = 1.061, P = 0.034), but these should not be regarded as independent confirmation. DGIdb analysis identified interactions between the genes of interest and various drugs or compounds. These findings provide exploratory genetic evidence linking circulating inflammatory proteins to AD, but robust replication was not established after multiple testing correction and requires further validation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270892","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":"β-Asarone Alleviates Post-stroke Neuroinflammation and Improves Mitochondrial Quality Via the BNIP3/BNIP3L-dependent Mitophagy Pathway.","authors":"Yujiao Wang, Daojun Xie, Yuhe Wang, Chengcheng Zhang, Zhuyue Chen","doi":"10.1007/s12035-026-06267-z","DOIUrl":"https://doi.org/10.1007/s12035-026-06267-z","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a leading cause of death and disability worldwide, with mitophagy playing a central role in post-stroke neurological dysfunction. β-Asarone, a major bioactive component derived from the traditional herb Acorus tatarinowii, possesses antioxidant, anti-inflammatory, and neuroprotective properties. However, whether β-asarone ameliorates IS by regulating mitophagy and its underlying mechanisms remains unclear. This study aimed to investigate whether β-asarone exerts neuroprotective effects against IS by modulating BNIP3/BNIP3L-mediated mitophagy. A middle cerebral artery occlusion (MCAO) rat model and an oxygen-glucose deprivation/reperfusion (OGD/R) cell model were established. Neuroprotective effects were evaluated using neurological behavioral scores, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, and Nissl staining. Mitochondrial function was assessed by measuring reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP). Mitophagy was observed via transmission electron microscopy (TEM) and fluorescence microscopy. Western blot (WB) analysis was performed to detect BNIP3/BNIP3L pathway proteins. Results showed that β-asarone enhanced mitophagy, improved mitochondrial function, and alleviated post-stroke neuroinflammation. Conversely, the autophagy inhibitor 3-methyladenine (3-MA) impaired mitophagic function, exacerbating ischemia-induced brain injury and inflammation, while β-asarone treatment reversed these detrimental effects. In summary, β-asarone mitigates neuroinflammation and neuronal injury after IS, at least partly through promoting BNIP3/BNIP3L-mediated mitophagy, highlighting this pathway as a promising therapeutic target for IS.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244731","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":"Comparative Hippocampal and Serum Metabolomics Reveals Dose-related Metabolic Alterations Consistent with TDMQ20 Intervention in a Cu-Aβ₄₂-induced Mouse Model.","authors":"Qureshi Ayesha, Yuan Sun, Jian Luo, Ying Yuan, Yan Liu, Qiong Liu, Jie Zhao, Liming Shen","doi":"10.1007/s12035-026-06286-w","DOIUrl":"https://doi.org/10.1007/s12035-026-06286-w","url":null,"abstract":"<p><p>Copper (Cu) dyshomeostasis and metabolic dysfunction have been implicated as key drivers of Alzheimer's disease (AD). Tetradentate monoquinoline 20 (TDMQ20), a Cu chelator, reportedly improves behavioral deficits in AD model mice, but its underlying metabolic mechanism is unclear. Here, we addressed this via untargeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) metabolomics in the hippocampus and serum of AD model mice induced by intrahippocampal injection of Cu amyloid-β₄₂ (Cu-Aβ₄₂) and then treated with TDMQ20 at low (LT, 5 mg/kg) and high (HT, 10 mg/kg) doses. Results showed that AD was associated with tissue-specific metabolic perturbations: hippocampal disorders were enriched in linoleic acid and glycerophospholipid metabolism, while serum perturbations centered on tryptophan, sphingolipid, and purine metabolism, with organic acids, lipids, and benzenoids as core differential metabolite classes. TDMQ20 reversed these abnormalities in a dose-associated manner: LT regulated tryptophan/linoleic acid metabolism in the hippocampus and purine/arachidonic acid metabolism in serum, while HT shifted the hippocampal metabolic profile substantially toward that of the control group. Cross-matrix analysis identified PS (15:0/22:0) and LPC (18:2/0:0) as key lipid metabolites with opposite expression patterns between hippocampus and serum, and four serum endogenous metabolites (pipecolic acid, PGG2, N-sulfo-D-glucosamine, and hex-2-ulose) as exploratory candidate metabolites. TDMQ20 was associated with metabolomic changes in both hippocampus and serum consistent with attenuated oxidative stress, neuroinflammation, and membrane lipid remodeling, suggesting preferential central metabolic modulation and dose-associated action. This study provides metabolomic evidence consistent with TDMQ20's potential tissue-resolved regulatory properties and identifies exploratory candidate metabolites for monitoring therapeutic efficacy in AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270836","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 of Cholinergic Stimulation with Improved Functional Performance and Neurotrophic Markers in Mild Cognitive Impairment.","authors":"Rizwan Qaisar, M Shahid Iqbal, Firdos Ahmad, Asima Karim","doi":"10.1007/s12035-026-06302-z","DOIUrl":"https://doi.org/10.1007/s12035-026-06302-z","url":null,"abstract":"<p><p>Mild cognitive impairment (MCI) is frequently accompanied by early impairment in gait and postural control. Whether commonly prescribed cognitive therapies differentially influence physical function and neurotrophic signaling remains unclear. We followed 99 older adults with MCI for six months while receiving either the cholinergic agent Donepezil (n = 47, age = 68.3 ± 4.1 years) or the glutamatergic modulator Memantine (n = 52, age = 70.1 ± 3.9 years). Postural balance and gait speed were assessed using the Short Physical Performance Battery. Plasma brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured. Donepezil treatment improved postural balance (Cohen's d = 0.30) and gait speed (d = 0.45), whereas Memantine produced no meaningful changes (d < 0.20 for both outcomes). Repeated-measures ANOVA demonstrated significant Time × Treatment interactions for balance (F(1,97) = 5.9, p < 0.05) and gait speed (F(1,97) = 6.4, p < 0.05). Plasma BDNF increased by approximately 22% (d = 0.46) and GDNF by 19% (d = 0.42) following Donepezil, with no significant biomarker changes in the Memantine group. In the Donepezil group, changes in BDNF correlated with improvements in balance (r2 = 0.13, p = 0.012) and gait speed (r2 = 0.12, p = 0.018), while GDNF changes correlated with balance (r2 = 0.10, p = 0.032) and gait speed (r2 = 0.19, p = 0.002). Multivariate regression analyses demonstrated independent associations of BDNF and GDNF with balance and selected functional outcomes after adjustment for confounders. Donepezil is associated with clinically meaningful improvements in mobility in MCI, accompanied by enhanced neurotrophic support. These findings are consistent with a relationship between cholinergic stimulation, motor function, and neurotrophic pathways in MCI.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245544","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":"Correction: Mast Cells in Neuroimmune Interactions: Mechanisms, Pathophysiological Roles, and Therapeutic Implications.","authors":"Ahmed Hasan, Abd Al Rahman Asfour, Hafsah Qaba, Amal A Al-Sharabi, Adel Asfoor, Sarhan Mohammed, Arwa Al-Adhreai, Selahaddin Güner, Mohammed ALSaeedy","doi":"10.1007/s12035-026-06276-y","DOIUrl":"https://doi.org/10.1007/s12035-026-06276-y","url":null,"abstract":"","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245489","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":"Opposing Patterns of the Histone Variant MacroH2A1.1 in Fmr1 Knockout and BTBR T+ Itpr3tf/J Mouse Models of Autism Spectrum Disorder.","authors":"Martin N Ivanov, Andon Mladenov, Desislava K Tsoneva, Alessandro Napoli, Tommaso Mazza, Anton B Tonchev, Irene Coppola, Valentina Chiodi, Anna Maria Tartaglione, Manlio Vinciguerra, Maria Rosaria Domenici","doi":"10.1007/s12035-026-06277-x","DOIUrl":"https://doi.org/10.1007/s12035-026-06277-x","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) exhibits substantial heterogeneity, wherein genetic and idiopathic forms may converge on shared core phenotypes through divergent molecular pathways. The histone variant macroH2A1.1, implicated in chromatin repression and DNA repair, has been linked to behavioral alterations opposite to core ASD features when depleted systemically. However, its regional and cell-type-specific regulation in genetic versus idiopathic ASD models remains unclear. We investigated macroH2A1.1 expression across the dorsal striatum, hippocampus, and medial prefrontal cortex in Fmr1 knockout (Fragile X syndrome model) and BTBR T+ Itpr3tf/J (idiopathic ASD model) mice. Quantitative PCR and imaging analyses revealed opposing patterns: BTBR mice showed region-specific mRNA downregulation and increased strongly stained macroH2A1.1-positive nuclei, whereas Fmr1 knockout mice exhibited reduced strong staining with increased weak staining, specific to neurons and not astrocytes, independent of significant mRNA changes. Bulk RNA-seq meta-analysis and pseudobulk single-cell transcriptomics further identified pathway-level enrichment of oxidative phosphorylation, chromatin remodeling, and transcriptional repression functional gene sets in unmatched public datasets (BTBR striatum; FXS hippocampus and cortex), with pronounced neuron-astrocyte divergence in Fmr1 knockout cortex. These findings underscore distinct epigenetic regulatory mechanisms in genetic and idiopathic ASD models.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245487","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":"Design and Synthesis of Novel β-Naphthol Dithiocarbamate Hybrids: A Convergent Multifaceted Approach Towards AChE and Amyloid-β Inhibition for Alzheimer's Disease.","authors":"Saswati Swagatika Sahoo, Pratap Kumar Sahu, Sudhir Kumar Paidesetty, Preetesh Kumar Panda, Aruna Ghose, Abhishek Mishra","doi":"10.1007/s12035-026-06271-3","DOIUrl":"https://doi.org/10.1007/s12035-026-06271-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an irreversible and chronic neurodegenerative disease, posing a growing global health burden, necessitating the development of multitarget-directed ligands (MTDLs) to combat its complex, multifactorial pathology. In this research, a new series of β-naphthol-based dithiocarbamate derivatives (5a-5g) were designed, synthesized using a rational drug design approach, and their structures were elucidated using FTIR, UV, and NMR spectra analysis. Reportedly, compound 5d showed characteristic C-N, C = S, and C-S vibrations in FTIR, while distinct aromatic and piperidinyl proton signals were detected in NMR. The compounds were screened for pre-ADME, molecular docking, and DFT study. The in silico studies predicted favorable binding capabilities against acetylcholinesterase (AChE) and amyloid-β (Aβ) targets. The antioxidant and biochemical estimation of the synthesized β-naphthol-based dithiocarbamate derivatives was evaluated using several in vitro assays, among which compound 5d exhibited the highest free radical scavenging activity and anti-AChE activity (IC₅₀ = 3.54 ± 0.98 µg/mL). Neurobehavioral activity showed improved learning and memory during behavioral assessments of the streptozotocin (STZ)-induced rat model. Compound 5d (30 mg/kg) improved learning and memory in STZ-induced rats, supported by enhanced antioxidant enzyme levels and reduced oxidative stress markers. It also decreased Aβ_1-42 and AChE contents, with histopathological findings confirming significant neuroprotection in the hippocampus. The neuroprotective action of the β-naphthol-based dithiocarbamate derivative is likely associated with its combined antioxidant, cholinergic, and anti-Aβ properties. Collectively, these findings will provide a strong rationale for the futuristic clinical applicability of 5d as a potent therapeutic candidate for AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":"63 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149245477","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}