Metabolic brain disease最新文献

{"title":"Serum miR-329-3p as a potential biomarker for ischemic stroke: clinical association and in vitro neuroprotection via PTPN1.","authors":"Haitao Fang, Qi Zhou, Huihui Wang, Liping Wang, Hongyu Li","doi":"10.1007/s11011-026-02005-5","DOIUrl":"https://doi.org/10.1007/s11011-026-02005-5","url":null,"abstract":"<p><p>Ischemic stroke, a prevalent disorder of the cerebral vasculature, is associated with substantial risks of long-term disability and death. Explore the expression profile, diagnostic and prognostic relevance, and underlying molecular mechanisms of miR-329-3p in ischemic stroke. 126 acute ischemic stroke patients and 92 healthy controls were enrolled. Serum miR-329-3p and PTPN1 mRNA were measured by qRT-PCR. Neurological function was evaluated via NIHSS and 3-month mRS scores. In vitro, OGD/R-induced SH-SY5Y cells were used. Cell proliferation, apoptosis, oxidative stress, inflammation, and PI3K/Akt pathway activity were assessed. The miR-329-3p-PTPN1 interaction was validated, and rescue experiments were performed. miR-329-3p was downregulated in stroke patients, showing good diagnostic efficacy, and negatively correlated with NIHSS and mRS scores. miR-329-3p is significantly associated with the prognosis of patients. In OGD/R cells, miR-329-3p overexpression improved proliferation, reduced apoptosis, alleviated oxidative stress and inflammation, and activated PI3K/Akt. PTPN1 was confirmed as a direct target; its overexpression abolished the neuroprotective effects of miR-329-3p. Serum miR-329-3p is a potential diagnostic and prognostic biomarker for ischemic stroke and exerts in vitro neuroprotection by targeting PTPN1.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224539","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":"Chaihu-Jia-Longgu-Muli Tang ameliorates chronic restraint stress-induced depressive-like behaviors in association with modulation of the gut microbiota-NLRP3 inflammasome-microglia axis.","authors":"Baoying Wang, Xinyu Yang, Zhe Xie, Zibo Li, Xiangli Yan, Yucheng Li, Ming Bai, Erping Xu","doi":"10.1007/s11011-026-01971-0","DOIUrl":"https://doi.org/10.1007/s11011-026-01971-0","url":null,"abstract":"<p><p>Chronic stress-induced neuroinflammation and gut microbiota dysbiosis have been implicated in the pathogenesis of depression. The classic herbal formula Chaihu-Jia-Longgu-Muli Tang (CLM) has been reported to exert antidepressant effects, but the underlying mechanisms remain poorly understood. This study aimed to investigate whether CLM ameliorates depressive-like behavior in chronic restraint stress (CRS)-induced mice and to explore its association with the gut microbiota remodeling, NLRP3 inflammasome signaling, and microglia activation. A mouse model of depression was established through exposure to CRS. Depressive-like behaviors were assessed using the sucrose preference test (SPT), tail suspension test (TST), and open field test (OFT). Hippocampal neuronal damage was evaluated by HE and Nissl staining. Intestinal barrier integrity was examined by HE staining and immunofluorescence staining for ZO-1 and occludin. Colonic and hippocampal levels of pro-inflammatory cytokines were measured by ELISA. Gut microbiota composition was analyzed by 16 S rRNA gene sequencing. Hippocampal M1 microglial polarization and microglial NLRP3 localization were assessed by Iba-1/CD86 and Iba-1/NLRP3 double immunofluorescence staining, and NLRP3 inflammasome-related protein expression was further evaluated by Western blotting. CLM attenuated CRS-induced depressive-like behaviors and hippocampal neuronal damage, restored gut barrier integrity as indicated by increased ZO-1 and occludin expression and reduced colonic IL-6, TNF-α, and IL-1β levels, and reshaped the gut microbiota by increasing SCFA-producing Muribaculaceae, Alloprevotella, and Bacteroides and decreasing Dubosiella and Lactobacillus spp. Exploratory Spearman analyses identified several nominal associations between microbial taxa and behavioral or inflammatory variables; however, these associations did not remain significant after Benjamini-Hochberg FDR correction and should therefore be interpreted as hypothesis-generating. CLM-H also reduced hippocampal CD86⁺/Iba-1⁺ cells, decreased NLRP3⁺/Iba-1⁺ co-localization, and reduced NLRP3, caspase-1 p20, and pro-IL-1β expression. CLM-H ameliorates CRS-induced depressive-like behavior and neuronal damage in association with modulation of the gut microbiota composition, NLRP3 inflammasome-related signaling, and microglial activation. These findings support the potential of CLM as a multi-target intervention for depression-related phenotypes, while further causal validation is still required.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224533","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":"Quassin ameliorates acute cerebral infarction with attenuation of NF-κB signaling and neuroinflammation.","authors":"Zhaoliang Luo, Xu Zhang, Jiaolu Liao, Yuan Zhou, Yangxi Mao, Jun Tang","doi":"10.1007/s11011-026-01992-9","DOIUrl":"https://doi.org/10.1007/s11011-026-01992-9","url":null,"abstract":"<p><p>Acute cerebral infarction is a severe cerebrovascular disease characterized by neuronal injury, oxidative stress, and neuroinflammatory activation. Quassin is a bioactive quassinoid isolated from Quassia amara with reported antioxidant and anti-inflammatory activities; however, its protective effects against cerebral ischemic injury and the underlying mechanisms remain to be further clarified. In this study, middle cerebral artery occlusion/reperfusion rat models and oxygen-glucose deprivation/reoxygenation models in bEnd.3 brain microvascular endothelial cells were established to evaluate the neuroprotective effects of Quassin. Neurological deficit scoring and hematoxylin-eosin staining were used to assess neurological dysfunction and brain histopathological injury. Cell viability was detected using the Cell Counting Kit-8 assay. Inflammatory cytokines were measured by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, intracellular reactive oxygen species were detected by DCFH-DA staining and flow cytometry, and nuclear factor kappa B pathway activation was analyzed by immunohistochemistry and Western blotting. Quassin markedly improved neurological deficits, alleviated brain histopathological damage, and restored cell viability after ischemic injury. Moreover, quassin reduced reactive oxygen species accumulation and decreased the expression of interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and inducible nitric oxide synthase. At the molecular level, quassin reduced the phosphorylation of IκBα and p65, consistent with attenuated NF-κB signaling activation. The nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate further supported the involvement of this pathway. These findings suggest that the protective effects of quassin against cerebral ischemic injury are associated with reduced oxidative stress, neuroinflammation, and NF-κB signaling activation.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216473","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":"Exploring the potential of resveratrol-enriched cord mesenchymal stem cell derived exosomes in an in vitro Parkinson's model.","authors":"Suhair Rami Mohammed Shamshir, Gulen Melike Demirbolat, Sevim Isik","doi":"10.1007/s11011-026-02003-7","DOIUrl":"https://doi.org/10.1007/s11011-026-02003-7","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the pathological aggregation of α-synuclein (α-syn) into Lewy bodies and it is known as the second most prevalent neurodegenerative disorder. The pathogenesis of PD involves mitochondrial dysfunction, oxidative stress, impaired protein degradation, and neuroinflammation. Current therapeutic strategies are largely symptomatic and remain limited in their ability to halt disease progression. Resveratrol (Res) has been shown to mitigate oxidative stress, preserve mitochondrial integrity, and reduce α-syn aggregation in PD models due to its antioxidant and neuroprotective properties. Despite its promising therapeutic potential, its poor bioavailability and rapid metabolism hinder the achievement of the desired therapeutic effects, which calls for advanced drug delivery systems. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) exosomes (Exos) are nanoscale extracellular vesicles with intrinsic neuroprotective, anti-inflammatory, and regenerative properties. They represent a promising carrier system owing to biocompatibility and the ability to cross the blood-brain barrier. Since the isolation technique is a critical parameter affecting both Exos yield and therapeutic efficacy, the study initially focused on optimizing the isolation process through a comparative investigation of ultracentrifugation and commercial isolation kits. Exos obtained with the highest yield and optimal characteristics, were subsequently subjected to Res loading through the probe sonication method. After the physicochemical characterization of Res-loaded exosomes (Exo-Res), their therapeutic potential was evaluated in an in vitro PD model established by rotenone-induced neurotoxicity in SH-SY5Y cells. Cell viability, oxidative stress, mitochondrial function, and whole protein aggregation were comprehensively assessed. Exo-Res isolated with Kit-1 showed a smaller particle size (94.0 nm) with high homogeneity (PDI < 0.3), high yield (3.9 × 10¹¹ particles/mL), and good entrapment efficiency (58.3%). It released Res in a sustained manner over 4 h. Our findings confirmed that Exo-Res significantly reduced whole protein aggregation mitigated oxidative stress, enhanced neuronal survival, and preserved mitochondrial function more effectively than either free Res or unloaded Exos. These results show that Exo-Res is a promising biocompatible nanocarrier-based therapeutic strategy for PD and possibly other neurodegenerative disorders, overcoming the key challenge of Res bioavailability while benefiting from the biocompatibility and therapeutic performance of exosomes.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195304","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":"The small giant actor in the pathogenesis of neurodegenerative diseases: Microtubules.","authors":"Aslı Aksoy Gündoğdu, Neslihan Gücüyener Özkan, Demet Özbabalık Adapınar","doi":"10.1007/s11011-026-02001-9","DOIUrl":"https://doi.org/10.1007/s11011-026-02001-9","url":null,"abstract":"<p><p>Neurodegenerative diseases are a clinically and pathologically diverse group of disorders characterized by progressive neuronal dysfunction, synaptic impairment, and neuronal loss. Although research has traditionally focused on disease-associated protein misfolding and aggregation, increasing evidence implicates abnormalities of cytoskeletal organization and intracellular transport in several neurodegenerative conditions. Microtubules contribute to neuronal polarity, axonal and dendritic transport, organelle distribution, and synaptic maintenance. These functions are regulated in part by tubulin isotypes, post-translational modifications collectively described as the tubulin code, microtubule-associated proteins, and molecular motors. This narrative review examines evidence linking alterations in these processes with Alzheimer's disease, Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, and prion disease. We summarize proposed interactions among microtubule instability, impaired axonal transport, mitochondrial dysfunction, and disease-associated proteins, including tau, α-synuclein, mutant huntingtin, TDP-43, and prion protein. Evidence connecting tau pathology with microtubule dysfunction is comparatively well established in Alzheimer's disease and MAPT-related tauopathies, whereas findings in other disorders are more heterogeneous and are frequently derived from cellular or animal models. We also discuss emerging experimental approaches, candidate biomarkers, and investigational microtubule-directed treatments. However, no tubulin-specific biomarker or microtubule-targeted disease-modifying treatment discussed in this review has yet been clinically validated. Overall, microtubule dysfunction may represent one component of broader, disease-specific pathological networks rather than a universal primary cause of neurodegeneration. Further longitudinal and clinical studies are needed to determine whether microtubule-related alterations act as causes, consequences, or modifiers of disease progression.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183080","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":"Gentiopicroside alleviates depression-like symptoms in animal models through regulating COX-2-mediated autophagy and inflammation.","authors":"Wei Ke, Gaoli Liu, Mengjuan Lin, Tao Yao, Chunping He","doi":"10.1007/s11011-026-01888-8","DOIUrl":"https://doi.org/10.1007/s11011-026-01888-8","url":null,"abstract":"<p><p>Depression is a serious mental illness affecting millions of people worldwide. This study investigates the effects of gentiopicroside, a compound found in traditional Chinese medicine, on depression-like animal models and its potential mechanism of action. The study utilized rat models with corticosterone-induced depression and treated them with various concentrations of gentiopicroside. The effects on hippocampal cells, serum 5-HT levels, inflammation, autophagy, and oxidative stress markers were observed. The role of Cyclooxygenase-2 (COX-2) expression and mitophagy was also examined using in vitro neuron cell models. Gentiopicroside demonstrated dose-dependent effects on alleviating hippocampal cell damage, restoring serum 5-HT levels, and inhibiting inflammation and oxidative stress markers. It also promoted autophagy and modulated COX-2 expression in the rat models. The in vitro study revealed that gentiopicroside could regulate COX-2 expression, reduce mitochondrial membrane potential loss and cell apoptosis, and inhibit NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammatory complex-related proteins and cytokines. Overexpression of COX-2 significantly reversed the positive effects of gentiopicroside, while PINK1 (PTEN-induced kinase 1) overexpression promoted mitophagy, inhibited NLRP3 inflammatory complex activation, and reduced oxidative stress. Gentiopicroside ameliorates depression-like symptoms in animal models by suppressing COX-2 expression. This suppression is necessary for the subsequent enhancement of PINK1-mediated mitophagy, which helps to re-establish mitochondrial homeostasis and attenuate neuroinflammation and oxidative stress. This novel mechanism may potentially lead to the development of new therapies for depression treatment.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183066","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":"Cerebrospinal fluid amino acid alterations are associated with oxidative stress and neuronal injury markers in multiple sclerosis.","authors":"Radka Bartová, Darina Slezáková, Monika Ďurfinová","doi":"10.1007/s11011-026-02007-3","DOIUrl":"https://doi.org/10.1007/s11011-026-02007-3","url":null,"abstract":"<p><p>Altered glutamatergic neurotransmission and oxidative stress are implicated in the pathophysiology of multiple sclerosis (MS), yet their interplay remains incompletely understood. This study investigated cerebrospinal fluid (CSF) levels of neuroactive amino acids (aspartate, glutamate, glycine, γ-aminobutyric acid) in relation to markers of lipid peroxidation, antioxidant capacity, and neuronal injury. Amino acids were quantified using a validated high-performance liquid chromatography method with fluorescence detection. Aspartate levels were significantly elevated in MS compared with other neurological diseases (ONDs), while glutamate showed a non-significant trend toward higher concentrations. Glycine concentrations were significantly higher in MS and RR-MS than in the non-neurological control group (CG), whereas GABA showed no significant group differences. Correlation analyses revealed a positive association between glutamate and 8-iso-PGF₂α in MS and RR-MS, whereas the correlation between aspartate and 8-iso-PGF₂α was observed only in ONDs and was based on a small number of observations (n = 6). Glycine showed a significant negative association with neuron-specific enolase in MS and RR-MS, while a positive association with total antioxidant status was observed in CG. These associations should be considered exploratory and do not establish causal or mechanistic relationships. The SP-MS subgroup showed the highest median concentrations of 8-iso-PGF₂α and MDA, while TAS was lower than in RR-MS; however, these findings were based on limited numbers of observations and should therefore be considered exploratory. These biochemical changes were observed in the absence of marked abnormalities in the measured CSF indicators of intrathecal IgG synthesis or blood-CSF barrier function. Together, these findings indicate associations between CSF amino acid homeostasis, oxidative stress and neuronal injury in MS. CSF amino acid profiling may provide complementary information on metabolic and neurotransmission-related alterations in MS and warrants further evaluation alongside established biomarkers in larger, independently characterized cohorts.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183083","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":"Blood-based multiplex nanobiosensing of Alzheimer's disease biomarkers: from nanoengineered ınterfaces to clinical translation.","authors":"Zilan Nupelda Pehlivan, Kaan Zıkşahna, Rumeysa Adıyıl, Murat Ihlamur","doi":"10.1007/s11011-026-01993-8","DOIUrl":"10.1007/s11011-026-01993-8","url":null,"abstract":"<p><p>Alzheimer's disease is a progressive neurodegenerative disorder in which molecular and cellular alterations begin years before clinical symptoms, creating a strong need for minimally invasive blood-based tools that can detect disease-related biomarkers with high analytical reliability. This structured narrative review examines recent advances in nanoengineered multiplex biosensors for ultrasensitive profiling of Alzheimer's disease biomarkers in blood-derived matrices. Particular emphasis is placed on amyloid-β 42/40 ratio, phosphorylated tau isoforms, neurofilament light chain, and glial fibrillary acidic protein, which collectively reflect amyloid pathology, tau-associated neurodegeneration, axonal injury, and glial activation. We discuss electrochemical, plasmonic, surface-enhanced Raman scattering, field-effect transistor, nanozyme-assisted, and lab-on-a-chip platforms, focusing on how nanoengineered interfaces improve bioreceptor immobilization, signal amplification, antifouling performance, and low-volume multiplex readout. Although many reported platforms achieve femtomolar to attomolar sensitivity and show potential for point-of-care or near-patient testing, their clinical translation remains constrained by plasma and serum matrix effects, nonspecific adsorption, multiplex channel cross-talk, inconsistent reporting of analytical limits, and batch-to-batch variability in nanomaterial fabrication. We further highlight the importance of matrix-matched calibration, standardized preanalytical workflows, interference testing, reproducibility across independent fabrication batches, and comparison with established clinical reference methods. Overall, nanoengineered multiplex biosensors represent a promising route toward accessible blood-based Alzheimer's disease biomarker profiling, but their implementation in clinical practice will require rigorous analytical validation, scalable manufacturing, and clinically meaningful assay design.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182919","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":"Inhibition of heparan sulfate synthesis by resveratrol in mucopolysaccharidosis type I and IIIB.","authors":"Estera Rintz, Aneta Szulc, Urszula Maliszewska, Grzegorz Węgrzyn","doi":"10.1007/s11011-026-01999-2","DOIUrl":"https://doi.org/10.1007/s11011-026-01999-2","url":null,"abstract":"<p><p>Mucopolysaccharidoses (MPS) are a group of pediatric disorders that are distinguished based on a lysosomal enzyme deficit leading to accumulation of glycosaminoglycans (GAGs). One of the GAGs is heparan sulfate (HS) which accumulates in cells inside the body, but the most devastating symptoms are caused by its accumulation in the central nervous system. Resveratrol, a natural compound, reduces the HS accumulation in both MPS I and MPS IIIB. In this study, we investigated the effects of resveratrol on HS metabolism in cellular models of MPS I and MPS IIIB, with particular focus on its role in GAG synthesis and degradation. Resveratrol treatment resulted in a consistent reduction of HS levels in both models, as confirmed by dot-blot analysis. To determine the underlying mechanism, we analyzed the expression of genes involved in GAG biosynthesis and turnover, as well as heparanase activity. The expression of key genes involved in the early stages of GAG biosynthesis was modulated by resveratrol, suggesting inhibition of substrate production. In contrast, expressions of genes associated with extracellular matrix remodeling and GAG turnover were largely unchanged in MPS I and only partially affected in MPS IIIB. Analysis of the heparanase enzyme activity showed no significant changes in either model. Although alterations in extracellular heparanase activity were observed in MPS IIIB cells, these changes were normalized rather than enhanced by resveratrol treatment. Our results indicate that resveratrol reduces HS accumulation through inhibition of synthesis rather than induction of unspecific degradation by heparanase, supporting its potential as a substrate-reduction strategy in MPS.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167322","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":"Olive leaf-derived exosome-like vesicles attenuate neurotoxicity in an in vitro rotenone model of Parkinson's disease.","authors":"Aya Sahsahi, Nurdan Sena Degirmenci, Mehtap Aydın, Fikrettin Şahin, Sevim Işık","doi":"10.1007/s11011-026-01990-x","DOIUrl":"https://doi.org/10.1007/s11011-026-01990-x","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by dopaminergic neuronal loss, oxidative stress, mitochondrial dysfunction, and protein aggregation. Despite extensive research, current therapeutic options remain limited to symptomatic management, underscoring the need for neuroprotective strategies targeting disease pathology. In this study, we investigated the neuroprotective potential of exosome-like vesicles derived from olive (Olea europaea) leaves (Ole-ELVs) in an in vitro PD model induced by rotenone in SH-SY5Y human neuroblastoma cells. To evaluate the protective impact of olive leaf-derived ELVs, oxidative stress, cell viability, mitochondrial function, and protein aggregation were assessed by measuring reactive oxygen species (ROS) levels, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, JC-1 mitochondrial membrane potential staining, and Thioflavin S staining for α-synuclein aggregation. Our findings indicate that treatment with Ole-ELVs significantly attenuated rotenone-induced ROS production, preserved mitochondrial membrane potential, and reduced protein aggregation. Collectively, these results suggest that Ole-ELVs exert neuroprotective effects through antioxidative, protection against cytotoxicity, and mitochondrial-stabilizing mechanisms, offering a promising natural nanoscale therapeutic candidate for PD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167877","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}