Redox Report最新文献

{"title":"Inhibition of oxidative stress and the Neuropilin-2-induced neuroinflammatory pathway by EMO ameliorates epileptic seizures in the preclinical model of epilepsy.","authors":"","doi":"10.1080/13510002.2026.2647496","DOIUrl":"10.1080/13510002.2026.2647496","url":null,"abstract":"","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2647496"},"PeriodicalIF":7.4,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative eustress is associated with AMPK and AKT activation, GLUT4 translocation and glucose uptake in skeletal muscle cells and fibres.","authors":"Eva Martín-Prieto, Leonardo A Catalano-Iniesta, Escarlata Fernández-Puente, Jesús Palomero","doi":"10.1080/13510002.2026.2721882","DOIUrl":"10.1080/13510002.2026.2721882","url":null,"abstract":"<p><p><b>Objectives:</b> Reactive oxygen and nitrogen species (RONS) act as signalling molecules under physiological conditions; however, how oxidative eustress regulates glucose uptake in skeletal muscle remains poorly defined. We investigated the role of moderate oxidation in skeletal muscle glucose uptake, focusing on AKT/AMPK phosphorylation, GLUT4 translocation and functional glucose uptake. <b>Methods:</b> AKT and AMPK phosphorylation were analysed in C2C12 myoblasts/myotubes exposed to insulin and redox-modulating stimuli associated with oxidative eustress, including hydrogen peroxide, nitric oxide donors and angiotensin II. GLUT4 translocation was assessed by quantitative immunocytochemistry and confocal fluorescence microscopy in cells expressing a GLUT4 reporter. Glucose uptake was evaluated in isolated skeletal muscle fibres using 6-NBDG. <b>Results:</b> Oxidative eustress was associated with increased AKT and AMPK phosphorylation and enhanced GLUT4 translocation to the plasma membrane. Hydrogen peroxide, nitric oxide donors and angiotensin II increased GLUT4 presence at the plasma membrane and enhanced glucose uptake, with hydrogen peroxide showing a dose-dependent effect. Increased glucose uptake was consistent with GLUT4 translocation. <b>Discussion:</b> These findings support oxidative eustress as a physiological redox mechanism linking AKT/AMPK activation, GLUT4 translocation and glucose uptake in skeletal muscle. Redox signalling may therefore contribute to skeletal muscle glucose metabolism.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2721882"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhaponticin alleviates pancreatic acinar cell necrosis by attenuating oxidative stress via modulation of the HIF-1α signaling pathway.","authors":"Xinyue Xie, Pei Yang, Shuai Wang, Xingmeng Xu, Liuhui Wang, Pin Li, Guotao Lu, Weiwei Chen, Runfeng Sun, Jingjing Zhang, Zhihao Wang","doi":"10.1080/13510002.2026.2663628","DOIUrl":"10.1080/13510002.2026.2663628","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigated the protective effects and mechanisms of rhaponticin (Rha) against acinar cell injury in acute pancreatitis (AP).</p><p><strong>Methods: </strong>Pancreatic acinar cell injury was induced using multiple in vitro and in vivo AP models. The mitochondrial function, necrosis, and oxidative stress were assessed. Network pharmacology and molecular docking were applied to predict potential molecular targets, which were subsequently validated experimentally. The involvement of hypoxia-inducible factor 1-alpha (HIF-1α) signaling and necroptosis-related proteins, including receptor-interacting protein kinase 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL), was further explored. Both pharmacological inhibition and siRNA-mediated knockdown were employed to verify the target specificity of Rha.</p><p><strong>Results: </strong>Rha treatment significantly preserved mitochondrial function, reduced ROS, and alleviated pancreatic injury. Network pharmacology and molecular dockingresults identified HIF -1a as the key target of Rha. Consistently, Rha treatment markedly downregulated HIF-1α expression and inhibited necroptosis by suppressing the activation of RIP3 and p-MLKL. Notably, neither pharmacological inhibition nor siRNA-mediated knockdown of HIF-1α produced additional protective effects in the presence of Rha, indicating the involvement of HIF-1α in mediating its actions.</p><p><strong>Conclusion: </strong>Rha effectively attenuates acinar cell necrosis and oxidative via the HIF-1α-mediated necroptosis pathway, highlighting Rha as a promising therapeutic candidate for AP.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2663628"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress in neurodegeneration: from a simple insult to a dynamic regulator.","authors":"Lan Zhang, Xinyue Zhai, Yalong Yan, Lihong Xiang, Yue Zhang, Xinying Zhou, Lianmei Cai, Zixi Tang, Yiyuan Xia","doi":"10.1080/13510002.2026.2654906","DOIUrl":"10.1080/13510002.2026.2654906","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the central role of oxidative stress in neurodegenerative diseases, and to explore its dynamic regulatory features, underlying signaling pathways, and molecular mechanisms, as well as advanced technological strategies for antioxidant intervention.</p><p><strong>Methods: </strong>This review comprehensively evaluated existing literature on oxidative stress in neurodegenerative diseases. It analyzed key regulatory pathways (Nrf2, Keap1, AMPK, mTOR) and molecular processes, including ferroptosis, NETosis, and mitochondrial quality control systems, along with oxidative damage to DNA, lipids, and proteins. The review also assessed advanced technological approaches such as subcellular organelle targeting, nanocarrier delivery systems (e.g. gold nanoparticles, liposomes for glutathione delivery), and single-cell/spatial omics technologies (e.g. single-cell redoxomics, spatial transcriptomics).</p><p><strong>Results: </strong>Oxidative stress exhibits dynamic features, generating protective signals in early stages but transitioning into destructive factors later. A major obstacle for current antioxidant therapies is the blood-brain barrier. Breakthrough strategies identified include precision targeting at the subcellular level, functionalized nanoparticles for efficient antioxidant delivery, and the integration of single-cell redoxomics with spatial transcriptomics to identify specific biomarkers and enable personalized treatments.</p><p><strong>Discussion: </strong>By integrating novel molecular mechanisms and advanced technological resources, this review redefines oxidative stress not as a singular event but as a complex, dynamically regulated system in neurodegenerative diseases. This reconceptualization provides new perspectives for developing targeted and personalized therapeutic interventions.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2654906"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRX5 as a critical driver of colorectal cancer stemness and tumorigenicity.","authors":"Sung Woo Lee, Sun-Ji Park, Ga Eun Lee, Su-Min Jung, Jaeyeon Lee, San Kwon, Eunbyul Yeom, Dong-Seok Lee, Eui-Hwan Choi","doi":"10.1080/13510002.2026.2673661","DOIUrl":"10.1080/13510002.2026.2673661","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells (CSCs) support colorectal cancer progression and therapy resistance, yet the redox regulators that sustain CSC identity are incompletely defined. We investigated the role of peroxiredoxin 5 (PRX5) in CSC formation and tumorigenicity using HCT116 colorectal cancer models.</p><p><strong>Methods: </strong>CSCs were enriched by serum-free spheroid culture and characterized by qPCR and western blotting for pluripotency and surface markers. PRX5 expression was regulated via siRNA or shRNA gene disruption and overexpression. Intracellular ROS was measured with DCF-DA staining. STAT3 activation was analyzed by <i>p</i>-STAT3 immunoblot. Functional assays included sphere formation, extreme limiting dilution analysis (ELDA), colony formation, and <i>in vivo</i> xenograft tumorigenicity in BALB/c-nu mice.</p><p><strong>Results: </strong>Spheroid induction selectively upregulated PRX5 among PRX isoforms. Efficient PRX5 knockdown (>95%) reduced OCT4, SOX2, NANOG, and CD133 expression, increased intracellular ROS, lowered <i>p</i>-STAT3 levels, and decreased sphere-forming frequency. Conversely, PRX5 overexpression enhanced pluripotency marker expression and proliferation. <i>In vivo</i>, PRX5-overexpressing xenografts grew faster, achieving a 2.5-fold greater tumor volume by day 19 and a 1.82-fold higher mean tumor weight compared with controls. Tumor tissues showed elevated OCT4, SOX2, NANOG, CD133, and EPCAM.</p><p><strong>Conclusion: </strong>PRX5 contributes to maintaining a redox environment associated with STAT3 activation and core stemness programs in CRC, promoting CSC phenotypes and tumorigenicity. Targeting PRX5-mediated redox signaling may warrant further investigation as a potential approach to disrupt CSC maintenance and overcome chemoresistance.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2673661"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147960195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin as a dynamic extracellular redox regulator: from Cys34 oxidation biomarkers to polysulfide-mediated homeostatic mechanisms and clinical applications.","authors":"Yu Ishima, Hiroshi Watanabe, Mayumi Ikeda-Imafuku, Hitoshi Maeda, Toru Maruyama, Masaki Otagiri, Victor T G Chuang","doi":"10.1080/13510002.2026.2682043","DOIUrl":"10.1080/13510002.2026.2682043","url":null,"abstract":"<p><p>Human serum albumin (HSA) is the most abundant circulating protein and a central mediator of extracellular redox homeostasis. Its antioxidant function has been attributed primarily to the free thiol at cysteine residue 34 (Cys34), whose progressive oxidation-yielding nonmercaptoalbumin isoforms HNA1 and HNA2-serves as a sensitive biomarker of systemic oxidative stress. Advances in electrospray ionisation time-of-flight mass spectrometry have enabled precise quantification of Cys34 modifications, establishing cysteinylated albumin as a clinically applicable marker in chronic kidney disease, chronic liver disease, diabetes, and ageing-related functional decline. Beyond its role as a biomarker, oxidized albumin is now recognized as an active pathogenic mediator in preclinical models, with emerging evidence implicating ferroptosis as a potential mechanism of renal tubular cell injury, and contributing to cardiovascular risk and sarcopenia. A previously unrecognized dimension of albumin redox biology has also emerged: the presence of endogenous oxidized polysulfide bonds (Ox-PSS; RSS_n-R', <i>n</i> > 1) across multiple intramolecular cysteine bridges. Quantified using the newly developed Elimination Method for Sulfide from Polysulfide, albumin polysulfides are dynamically regulated by oxidative stress and are significantly depleted in chronic kidney disease and early hepatitis, even when conventional Cys34-based markers remain unchanged. Polysulfide depletion impairs both Site II drug-binding capacity and reactive oxygen species scavenging activity, with direct implications for pharmacokinetics and therapeutic efficacy. These findings collectively reframe HSA as a dynamic polysulfide reservoir and extracellular redox regulator, highlighting albumin polysulfide modulation as a compelling emerging therapeutic strategy.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2682043"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13231813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1 gp120-induced lysosomal stress responses are controlled by TRPML1 redox sensors.","authors":"Nirmal Kumar, Braelyn Liang, Jonathan D Geiger","doi":"10.1080/13510002.2026.2679333","DOIUrl":"10.1080/13510002.2026.2679333","url":null,"abstract":"<p><strong>Background: </strong>Increased lysosomal stress responses (LSR) are commonly implicated in the pathogenesis of neurodegenerative disorders including HIV-1-associated neurocognitive disorders (HAND). The HIV-1 envelope glycoprotein gp120 causes LSR, increases levels of ferrous iron (Fe²⁺) in the cytosol and in mitochondria, disrupts the reactive species interactome (RSI), and increases neural cell death.</p><p><strong>Methods: </strong>Using SH-SY5Y human neuroblastoma and U87MG human astrocytoma cells treated with gp120 and pharmacological modulators, we evaluated redox signaling and LSR by redox-sensitive fluorescent probes, spinning-disk confocal microscopy, flow cytometry, Western blotting, and immunostaining.</p><p><strong>Results: </strong>Here, we report that TRPML1, an endolysosome redox-sensitive cation channel, is mechanistically involved in gp120-induced neurotoxicity. TRPML1 was activated by gp120-induced increases in cytosolic reactive oxygen species (ROS) and resulted in release of Fe²⁺ from endolysosomes in levels sufficient to increase cytosolic levels of Fe²⁺ and ROS as well as decrease levels of hydrogen sulfide (H₂S). Reduced glutathione normally buffers intracellular Fe²⁺, but gp120 decreased endolysosome glutathione levels and disrupted this regulatory control mechanism thereby promoting TRPML1-mediated Fe²⁺ efflux from endolysosomes. TRPML1 redox activation led to changes to the RSI in endolysosomes including increased ROS, lipid peroxidation, nitric oxide, and sulfane sulfur as well as decreased H₂S. These changes were accompanied by increased cysteine oxidation of luminal proteins and endolysosome deacidification. Pharmacological inhibition of TRPML1 or knocking down expression levels of TRPML prevented these effects.</p><p><strong>Conclusion: </strong>Our findings suggest that TRPML1 redox activation controls gp120-induced endolysosome dysfunction and iron/redox imbalance, and further implicates TRPML1 in the pathogenesis of HAND.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2679333"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein disulphide isomerase protects against ALS/FTD phenotypes associated with cyclin F in zebrafish and cellular models.","authors":"Sina Shadfar, Sonam Parakh, Emma Perri, Cyril Jones Jagaraj, Sara Assar Kashani, Keelin Beyers, Audrey M G Ragagnin, Angela S Laird, Julie D Atkin","doi":"10.1080/13510002.2026.2732775","DOIUrl":"https://doi.org/10.1080/13510002.2026.2732775","url":null,"abstract":"<p><strong>Background: </strong>Mutations in <i>CCNF</i>, encoding cyclin F, cause a small proportion of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases. Mutant cyclin F mislocalises from the nucleus to the cytoplasm, impairs the ubiquitin proteasome system, disrupts endoplasmic reticulum (ER) to Golgi transport, and triggers ER stress and apoptosis. Protein disulphide isomerase (PDI), a redox-active ER chaperone of the thioredoxin superfamily, protects against ALS phenotypes induced by mutant SOD1, TDP-43, and FUS, but its activity against mutant cyclin F has not been examined.</p><p><strong>Objectives: </strong>To test whether PDI overexpression prevents the cellular and behavioural phenotypes induced by the ALS/FTD-associated cyclin F^S621G mutation.</p><p><strong>Methods: </strong>Neuro-2a cells were co-transfected with mCherry-tagged wild-type or mutant cyclin F^S621G and V5-tagged PDI or empty vector. Subcellular localisation, XBP-1 and CHOP activation, proteasome reporter (GFPu) accumulation, nuclear morphology, and cleaved caspase-3 immunoreactivity were assessed by confocal microscopy. Transient transgenic zebrafish larvae generated by mRNA co-injection of cyclin F and PDI were assessed by photomotor response at 48 h post-fertilisation.</p><p><strong>Results: </strong>Mutant cyclin F^S621G induced cytoplasmic mislocalisation, ER stress (assessed by XBP-1 and CHOP activation), proteasome dysfunction (indicated by GFPu accumulation), and apoptosis (assessed by nuclear condensation and caspase-3 activation), all of which were significantly attenuated by PDI co-expression. Zebrafish larvae expressing cyclin F^S621G swam significantly shorter distances than uninjected or wildtype controls, and co-expression of PDI restored motor function to near-wildtype levels.</p><p><strong>Conclusion: </strong>PDI protects against ALS/FTD-associated mutant cyclin F in both cellular and <i>in vivo</i> zebrafish models, identifying PDI as a redox-based therapeutic target for <i>CCNF</i>-linked ALS/FTD.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2732775"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomics implicates NOX-driven redox imbalance in degenerative cervical myelopathy: findings from the Australian MYelopathy Natural History Registry [AO Spine RECODE-DCM research priority number 5].","authors":"Nashwa Najib, Valerie C Wasinger, Ryan O'Hare Doig, Muhammad Alsherbiny, Stone Sima, Ashish D Diwan","doi":"10.1080/13510002.2026.2649669","DOIUrl":"10.1080/13510002.2026.2649669","url":null,"abstract":"<p><strong>Objectives: </strong>To identify disease-relevant pathways and biomarkers in degenerative cervical myelopathy (DCM) patients from the MYelopathy Natural History Registry.</p><p><strong>Methods: </strong>Shotgun bottom-up proteomics (DCM <i>n</i> = 20; controls <i>n</i> = 20) was performed using LC-MS/MS in DDA mode. Peptides were eluted over 90 min on an in-house manufactured C18 column. Differential proteins were validated using parallel reaction monitoring (PRM) on the same instrument over a 60-min gradient. Bioinformatics was conducted in Skyline and ELISA using Ella™.</p><p><strong>Results: </strong>Discovery proteomics highlighted acute phase and cytokine signalling with STAT1/STAT3 involvement. Targeted assays showed higher IL-6 and IFN-γ in DCM, consistent with a pro-inflammatory state. PRM indicated upregulation of NADPH oxidase complex cytochrome b-245 α-chain (p22 phox or CYBA) and glutathione reductase, alongside downregulation of extracellular glutathione peroxidase, a pattern consistent with NOX-driven reactive oxygen species generation and impaired glutathione redox homeostasis. Together, this provides human plasma evidence of systemic redox imbalance in DCM and nominate a mechanistic framework linking cytokine signalling to oxidative stress via NOX activation and disrupted glutathione cycling.</p><p><strong>Conclusion: </strong>Findings support the feasibility of a plasma 'liquid biopsy' to augment diagnosis and monitoring. The modest cohort size and potential confounding by age and adiposity, absolute quantification, multivariate adjustment, and external validation are warranted to establish specificity and clinical utility.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2649669"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uric acid alleviates the inflammatory response in LPS-induced BV2 cells and MPTP-induced PD mice by resisting ferroptosis through the Nrf2 signalling pathway.","authors":"Dongmei Zhou, Tian Xiong, Bing Yang, Fanjie Liu, Xianglai Mo, Ting Chen, Peipei Lu, Xinghuan Liang, Li Li, Yingfen Qin, Decheng Lu, Feng Huang, Xi Yang","doi":"10.1080/13510002.2026.2668238","DOIUrl":"10.1080/13510002.2026.2668238","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation, oxidative stress, and ferroptosis are implicated in Parkinson' s disease (PD) pathogenesis. Epidemiological studies suggest that elevated uric acid (UA) levels may reduce PD risk, but the precise molecular mechanisms involved remain unclear. In this study, we investigated the effects of UA in lipopolysaccharide (LPS) or MPP+-stimulated BV2 microglia and MPTP-induced PD mouse models.</p><p><strong>Methods: </strong>BV2 cells are recognized as a standardized and reproducible neural inflammatory cell model for mechanism exploration. The anti-ferroptosis and anti-inflammatory effects of UA were assessed in LPS or MPP+ stimulated BV2 microglia and in an MPTP-induced PD mouse model. Western blot, qPCR, ELISA, and immunofluorescence were used to analyse the expression of inflammasome-related markers. ROS, MDA, GSH, and Fe²⁺ levels were measured using testing kits, while mitochondrial ultrastructure was evaluated through transmission electron microscopy. PD-related markers were assessed by ethology and immunohistochemistry. The Nrf2 inhibitor ML385 was employed to validate pathway specificity.</p><p><strong>Results: </strong>We found that UA treatment reduced the expression of proinflammatory cytokines (TNF-<i>α</i>, IL-6, and IL-1β), ROS production, lipid peroxidation, and intracellular Fe²⁺ in BV2 microglia while increasing the antioxidant capacity and preserving the mitochondrial ultrastructure. In MPTP-treated mice, UA improved motor performance, preserved dopaminergic neuron density in the substantia nigra, and reduced neuroinflammation. UA activated Nrf2 signalling and upregulated GPX4 expression, which were attenuated by ML385, confirming the Nrf2 dependence of these effects.</p><p><strong>Conclusion: </strong>UA alleviates ferroptosis and neuroinflammation in LPS or MPP+ stimulated BV2 microglia and MPTP-induced PD mouse models through the activation of the Nrf2 signalling pathway.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2668238"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}