Redox Biology最新文献

{"title":"Phactr4 promotes oxidative stress and behavioral disorder caused by chronic stress via regulating PP1/GSK3-β pathway","authors":"Tian Lan ,&nbsp;Ye Li ,&nbsp;Wanzhe Zhang ,&nbsp;Xiao Chen ,&nbsp;Mengni Chang ,&nbsp;Wenjing Wang ,&nbsp;Changmin Wang ,&nbsp;Shihong Chen ,&nbsp;Linghua Kong ,&nbsp;Shuyan Yu","doi":"10.1016/j.redox.2025.103873","DOIUrl":"10.1016/j.redox.2025.103873","url":null,"abstract":"<div><div>Oxidative stress, defined as a process triggered by an imbalance between the accumulation of free radicals and antioxidant defences, has been considered implicated in many neurological disorders, including major depressive disorder (MDD). In the present study, we demonstrated that the expression of phosphatase and actin regulatory factor 4 (Phactr4) was increased within the dentate gyrus (DG) region of the hippocampus of the chronic stress-induced depressive mice. Phactr4 has been shown to enhance oxidative stress in the brain by interacting with protein phosphatase 1 (PP1) and synergistically reducing the level of phosphorylation of glycogen synthase kinase 3β (GSK3β), thus enhance the susceptibility to stress stimulation in mice. Knocking down phactr4 in the hippocampal DG regions can suppressed GSK3β activation, alleviate oxidative stress, and further improve the depression-like behaviors in mice. More interestingly, we further found physical exercise can downregulate the level of Phactr4, reduce the accumulation of reactive oxygen species (ROS) in the brain, ameliorate neuronal damage, and reverse depressive-like behaviors in mice. These findings suggest that physical exercise may promote the restoration of oxidative stress in brain and ameliorates depressive behaviors in mice by down-regulating the Phactr4-PP1-GSK3β pathway.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103873"},"PeriodicalIF":11.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive in vivo discrimination between mitochondrial ROS and global ROS production in solid tumors using EPR spectroscopy","authors":"Barbara Mathieu ,&nbsp;Justin D. Rondeau ,&nbsp;Lionel Mignion ,&nbsp;Pierre Sonveaux ,&nbsp;Bernard Gallez","doi":"10.1016/j.redox.2025.103871","DOIUrl":"10.1016/j.redox.2025.103871","url":null,"abstract":"<div><div>Because the precise site of ROS production plays a key role in cellular redox signaling and its (patho)physiological consequences, it is crucial to develop tools that enable site-specific detection of ROS in complex systems, including <em>in vivo</em>. Here, we propose the use of Electron Paramagnetic Resonance (EPR) and dual nitroxide sensors composed of mitoTEMPO and carbamoyl-proxyl (3CP) to probe ROS production in the mitochondrial and intracellular/extracellular compartments, respectively. For the proof-of-concept, the decay rates of the nitroxides were measured in 4T1 breast tumor models, both <em>in vitro</em> and <em>in vivo</em>, using 9 GHz and 1 GHz spectrometers, respectively. To modulate the level of ROS either in the cytosol or in the mitochondria, cells and mice were treated with either the glutathione synthesis inhibitor <span>l</span>-Buthionine Sulfoximine (L-BSO) or Antimycin A, an inhibitor of the complex III of the mitochondrial electron transport chain, or their appropriate controls. In mice, an increase in relative decay rate was observed for 3CP, but not for mitoTEMPO, 1 and 2 days after starting L-BSO treatment, while the opposite result was obtained after Antimycin A treatment. These observations were consistent with results obtained on cells <em>in vitro</em>. <em>Ex-vivo</em> analyses of tumors, with or without ferricyanide that converts hydroxylamines back to nitroxides, revealed non-significant changes in the total amount of nitroxide + hydroxylamine, suggesting that the blood wash-out did not play a role in the decay of the nitroxide signal. In addition, the use of genetically engineered 4T1 cells that overexpress the mitochondrial isoform superoxide dismutase 2 (SOD2) allowed the assessment of the contribution of superoxide production to EPR signal decay. Overall, this study identifies a new protocol to noninvasively discriminate the site of ROS production <em>in vivo</em>.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103871"},"PeriodicalIF":11.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial MerTK impairment accelerates the development of atherosclerosis","authors":"Shijie Liu ,&nbsp;Jingke Yao ,&nbsp;Hongye Huang ,&nbsp;Xiaoyuan Bai ,&nbsp;Jinzi Wu ,&nbsp;Oishani Banerjee ,&nbsp;Zhicheng Jin ,&nbsp;Bingzhong Xue ,&nbsp;Hang Shi ,&nbsp;Zufeng Ding","doi":"10.1016/j.redox.2025.103861","DOIUrl":"10.1016/j.redox.2025.103861","url":null,"abstract":"<div><h3>Rationale</h3><div>Atherosclerosis is a chronic inflammatory disease primarily affecting large arteries and is the leading cause of cardiovascular disease. MER proto-oncogene tyrosine kinase (MerTK) plays a key role in regulating efferocytosis, a process for the clearance of apoptotic cells. This study investigates the specific contribution of endothelial MerTK to atherosclerosis development.</div></div><div><h3>Methods</h3><div>Big data analytics, human microarray analyses, proteomics, and a unique mouse model with MerTK deficiency in endothelial cells (<em>MerTK</em>^{<em>flox/flox</em>}<em>Tie2</em>^<em>Cr</em>e) were utilized to elucidate the role of endothelial MerTK in atherosclerosis development.</div></div><div><h3>Results</h3><div>Our big data analytics, encompassing approximately 98,881 cross analyses including 234 analyses for atherosclerosis in the aortic arch, along with human microarray data, reveal that inflammatory responses play a predominant role in atherosclerosis. In vivo, <em>MerTK</em>^{<em>flox/flox</em>}<em>Tie2</em>^<em>Cre</em> mice and the littermate control <em>MerTK</em>^{<em>flox/flox</em>} mice were used to establish an early stage of atherosclerosis model through a high-fat diet combined with AAV8-PCSK9 treatment. Consistent with big data analytics and human microarray analyses, our proteomics data showed that <em>MerTK</em>^{<em>flox/flox</em>}<em>Tie2</em>^<em>Cre</em> mice demonstrated significantly enhanced proinflammatory signaling, mitochondrial dysfunction, and activated mitogen-activated protein kinase (MAPK) pathway compared to that of <em>MerTK</em>^{<em>flox/flox</em>} mice. Endothelial MerTK deficiency induces endothelial dysfunction (enhanced endothelial inflammation, mitochondrial dysfunction, and activation of NADPH oxidases and MAPK signaling pathways) and subsequently causes smooth muscle cell (SMC) phenotypic alterations, ultimately promoting atherosclerosis development. The mechanism studies showed that the miR-218–5p/EC^MerTK/MAPK axis may play an important role in endothelial MerTK-mediated atherosclerosis.</div></div><div><h3>Conclusions</h3><div>Our findings provide strong evidence that endothelial MerTK impairment serves as a novel mechanism in promoting atherosclerosis development.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103861"},"PeriodicalIF":11.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-GPX4 drives a sustained drug-tolerant persister state in TNBC by a targetable adaptive FSP1 upregulation","authors":"Nazia Chaudhary ,&nbsp;Dibita Mandal ,&nbsp;Bhagya Shree Choudhary ,&nbsp;Sushmita Patra ,&nbsp;Darshan Jain ,&nbsp;Pritam Poonia ,&nbsp;Shagufa Shaikh ,&nbsp;Siddhi Tekalkar ,&nbsp;Shivani Malvankar ,&nbsp;Anusha Shivashankar ,&nbsp;Eeshrita Jog ,&nbsp;Leena Pilankar ,&nbsp;Rahul Thorat ,&nbsp;Vaishali V. Kailje ,&nbsp;Sonal Khanna ,&nbsp;Subhakankha Manna ,&nbsp;Bushra K. Khan ,&nbsp;Anjana Jadhav ,&nbsp;Kedar Sharma ,&nbsp;Soundharya Ramu ,&nbsp;Nandini Verma","doi":"10.1016/j.redox.2025.103864","DOIUrl":"10.1016/j.redox.2025.103864","url":null,"abstract":"<div><div>Metastatic relapses in Triple-Negative Breast Cancer (TNBC) patients with residual disease pose a significant clinical challenge. In this study, we longitudinally modelled cellular state transition from dormant drug-tolerant persister (DDTP) to proliferative (PDTP) cell state across TNBC subtypes. We identified specific molecular and phenotypic alterations that characterize the DTP states in TNBC cells that are maintained upon re-gaining proliferation. We found that Basal-Like proliferative DTPs stably acquired mesenchymal traits, while luminal androgen receptor-positive TNBC DTPs undergo partial Epithelial-to-Mesenchymal Transition (EMT). TNBC DTP cells exhibit reduced expression of glutathione peroxidase-4 (GPX4), conferring susceptibility to ferroptosis inducers. Mechanistically, GPX4 downregulation promotes EMT in TNBC, supported by an inverse correlation between GPX4 and EMT marker vimentin (VIM) expression that also serves as a predictor of survival in TNBC patients undergoing chemotherapy. The genetic, pharmacological, or chemotherapy-induced suppression of GPX4 in TNBC cells leads to robust upregulation of ferroptosis suppressor protein-1 (FSP1). The clinical significance of these findings is established by a strong predictive value of FSP1^high/VIM^high signature for worst survival and incomplete pathological response in chemotherapy-treated TNBC patients. Further, targeting FSP1 re-sensitizes cells to chemotherapy, while combined inhibition of FSP1 and GPX4 is selectively lethal in proliferative DTP TNBC cells by inducing ferroptosis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103864"},"PeriodicalIF":11.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artesunate induces ferroptosis in gastric cancer by targeting the TFRC-HSPA9 axis for iron homeostasis regulation","authors":"Yi Liu ,&nbsp;You Yu ,&nbsp;Zhihong Luo ,&nbsp;Ruoxin Fang ,&nbsp;Xiaodong Zhang ,&nbsp;Zhengkai Liao ,&nbsp;Wenhua Li","doi":"10.1016/j.redox.2025.103867","DOIUrl":"10.1016/j.redox.2025.103867","url":null,"abstract":"<div><div>Ferroptosis, a recently characterized form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a promising therapeutic strategy for cancer treatment due to its potential for selectively targeting cancer cells. Exploiting FDA-approved drugs to induce ferroptosis offers a novel approach that exploits cancer cells' vulnerabilities in iron metabolism and oxidative stress. Here, we identify artesunate, an antimalarial drug, as a potent inducer of ferroptosis in gastric cancer cells and reveal the transferrin receptor (TFRC) as a key mediator in this process. Notably, our study is the first to demonstrate an interaction between artesunate and TFRC through molecular docking and surface plasmon resonance (SPR) experiments, highlighting a novel mechanism by which artesunate stabilizes TFRC by inhibiting its lysosomal degradation. This stabilization is regulated via the heat shock protein HSPA9, another previously unreported interaction. Disrupting the TFRC-HSPA9 interaction facilitates iron accumulation and lipid peroxidation, hallmark features of ferroptosis, leading to significant cancer cell death. Additionally, in vivo studies confirm artesunate's anti-tumor efficacy, showing marked tumor growth inhibition and minimal systemic toxicity. These findings underscore the therapeutic relevance of targeting ferroptosis in cancer, particularly by leveraging TFRC's role in iron homeostasis. Furthermore, this study expands the understanding of post-translational regulation in ferroptosis, offering a new perspective on the role of artesunate in cancer therapy.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103867"},"PeriodicalIF":11.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"N-butylphthalide (NBP) and ligustrazine (TMP) triazole hybrids target the KEAP1-NRF2 pathway to inhibit ferroptosis and exert brain neuroprotectivity\" [Redox Biol. 86, (2025), 103835].","authors":"Guangyu Li,Haiyan Xiao,Chenwei Zuo,Haochen Xie,Xiaolin Wang,Jiaxin Wang,Ying Liu,Quanxing Hou,Guibo Sun,Yu Tian","doi":"10.1016/j.redox.2025.103860","DOIUrl":"https://doi.org/10.1016/j.redox.2025.103860","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"32 1","pages":"103860"},"PeriodicalIF":11.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen sulfide inhibits recruitment of monocyte-derived tumor associated macrophages in glioblastoma by downregulating CXCL12","authors":"Joseph Camarano ,&nbsp;Morgan Roque ,&nbsp;Gabrielle Gahn ,&nbsp;Stephen Garrett Whipple ,&nbsp;Danielle Terrell ,&nbsp;Charles Ronkon ,&nbsp;Jamie Toms ,&nbsp;Anthony Sin ,&nbsp;Bharat Guthikonda ,&nbsp;Khatri Latha ,&nbsp;Yuhui Yang ,&nbsp;Xinggui Shen ,&nbsp;Christopher G. Kevil ,&nbsp;Ganesh Rao ,&nbsp;Sungho Lee","doi":"10.1016/j.redox.2025.103866","DOIUrl":"10.1016/j.redox.2025.103866","url":null,"abstract":"<div><div>Tumor associated macrophages (TAMs) directly contribute to the dismal prognosis of glioblastoma by preventing anti-tumor immunity and promoting tumor invasion and angiogenesis. Inhibiting TAM infiltration is a potential therapeutic strategy in glioblastoma, with several chemokine antagonists in early clinical development. Hydrogen sulfide, a gasotransmitter that regulates microglial accumulation in a wide range of CNS diseases, may be a novel therapeutic target to prevent TAM recruitment in glioblastoma. In this study, hydrogen sulfide concentrations were directly measured from 14 isocitrate dehydrogenase (IDH)-wildtype glioblastoma surgical samples and compared against overall survival as well as expression of TAM markers and chemokines. Effects of hydrogen sulfide donor therapy on survival and TAM recruitment were also examined in a genetically engineered mouse model of glioblastoma. High hydrogen sulfide concentrations conferred a survival benefit in IDH-wildtype glioblastoma, in association with reduced monocyte-derived TAM density and downregulation of CXCL12. These findings were validated by administering hydrogen sulfide donor SG1002 to an immunocompetent mouse model of glioblastoma, which improved survival, inhibited monocyte infiltration, and downregulated CXCL12. Finally, hydrogen sulfide donor treatment directly reduced CXCL12 expression in glioblastoma cells, diminishing their ability to recruit monocytes in vitro. Taken together, these results demonstrate that hydrogen sulfide signaling prevents monocyte-derived TAM accumulation in glioblastoma by inhibiting chemotaxis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103866"},"PeriodicalIF":11.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon ion combined photon radiotherapy induces ferroptosis via NCOA4-mediated ferritinophagy in glioblastoma","authors":"Li Chen ,&nbsp;Wanzun Lin ,&nbsp;Ziyu Le ,&nbsp;Fangzhu Wan ,&nbsp;Haojiong Zhang ,&nbsp;Shikai Geng ,&nbsp;Qingting Huang ,&nbsp;Jing Gao ,&nbsp;Wei Hu ,&nbsp;Huaiyuan Chen ,&nbsp;Xingyu Liu ,&nbsp;Chunlin Shao ,&nbsp;Fengtao Su ,&nbsp;Jiade J. Lu ,&nbsp;Lin Kong","doi":"10.1016/j.redox.2025.103865","DOIUrl":"10.1016/j.redox.2025.103865","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most prevalent and lethal primary malignancy of the central nervous system, remains refractory to conventional photon radiotherapy due to inherent limitations in dose distribution. Although carbon ion radiotherapy offers distinct advantages, including its characteristic Bragg peak deposition and superior relative biological effectiveness, its clinical application is constrained by high costs and increased toxicity. This study explores the radiobiological interactions underlying a mixed carbon ion-photon irradiation regimen, a promising strategy in advanced particle therapy. Our findings demonstrate that combined irradiation exerts synergistic cytotoxic effects in GBM models. Mechanistic analysis reveals that this combination induces clustered DNA double-strand breaks, leading to the cytoplasmic accumulation of double-stranded DNA (dsDNA) fragments. This, in turn, activates the cGAS-STING-mediated cytosolic DNA sensing pathway, which facilitates NCOA4-FTH1 axis-driven ferritinophagy and ultimately triggering iron-dependent ferroptosis. These findings offer a new mechanistic perspective on optimizing combined particle therapy regimens for GBM treatment, with significant implications for translational applications in clinical radiation oncology.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103865"},"PeriodicalIF":11.9,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to an environmentally relevant mixture of polychlorinated biphenyls affects mitochondrial bioenergetics and plasticity","authors":"Maria Carolina Peixoto-Rodrigues ,&nbsp;Vladimir Pedro Peralva Borges-Martins ,&nbsp;José Raphael Monteiro-Neto ,&nbsp;Bruno Vicente ,&nbsp;Lucas José Guimarães ,&nbsp;Clara Fernandes-Carvalho ,&nbsp;Antonio Galina ,&nbsp;Victor Midlej ,&nbsp;Michal Toborek ,&nbsp;Rachel Ann Hauser-Davis ,&nbsp;Daniel Adesse","doi":"10.1016/j.redox.2025.103862","DOIUrl":"10.1016/j.redox.2025.103862","url":null,"abstract":"<div><div>Adaptations of cells to environmental insults typically require tightly regulated processes to preserve the organismal steady state, particularly in metabolically active cells such as neural cells. Polychlorinated biphenyls (PCBs) are persistent organic pollutants widely recognized for their neurotoxic potential. Due to their lipophilic nature, these compounds readily accumulate in the brain, where they can disrupt neuronal homeostasis. Herein, we examined the effects of exposure to an environmentally relevant PCB mixture on mitochondrial dynamics, ultrastructure, and function in the mouse neuroblastoma Neuro2a cell line. Ultrastructural examinations indicated evident signs of mitochondrial damage, including swelling, cristae disruption, and increased frequency of autophagic structures. Quantification of mitochondrial networks confirmed a shift from tubular to fragmented morphologies, accompanied with the modulation of the gene expression of genes involved in mitochondrial fusion and fission. Specifically, mitofusin 2 protein levels were increased at 24 and 48 h of treatment, and OPA1 at 48 h, whereas Drp1, phosphorylated at Ser616 was increased at 24 h. Markers of mitophagy PINK1 and Parkin were elevated at 72 and 48 h of exposure, respectively, whereas Atg5 and Atg7, markers of autophagy were increased at 24 h. We observed a decrease in mitochondrial membrane potential and increase in mtDNA levels in PCB-treated cultures at 24 h. Oxidative stress was also implicated by overexpression and increased enzymatic activity of superoxide dismutase 1 (SOD1). Functional tests revealed a transient impairment of mitochondrial respiration and ATP synthesis, which was later restored, pointing to the recruitment of compensatory mechanisms. Together, these results indicate that PCB exposure activates an integrated stress response with oxidative imbalance, mitochondrial bioenergetics, remodeling, and autophagy features, revealing the neural cell vulnerability and plasticity to environmental insult.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"87 ","pages":"Article 103862"},"PeriodicalIF":11.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoskeletal disruption-induced calcium dysregulation drives cell death in anti-IgLON5 disease","authors":"Lisanne Korn ,&nbsp;Júlia Csatári ,&nbsp;Andreas Schulte-Mecklenbeck ,&nbsp;Laura Vinnenberg ,&nbsp;Nadine Ritter ,&nbsp;Paul Disse ,&nbsp;Isabel Aymanns ,&nbsp;Jan D. Lünemann ,&nbsp;Catharina C. Gross ,&nbsp;Petra Hundehege ,&nbsp;Guiscard Seebohm ,&nbsp;Heinz Wiendl ,&nbsp;Thilo Kaehne ,&nbsp;Matthias Pawlowski ,&nbsp;Stjepana Kovac","doi":"10.1016/j.redox.2025.103854","DOIUrl":"10.1016/j.redox.2025.103854","url":null,"abstract":"<div><div>Anti-IgLON5 disease is an autoimmune encephalitis with more chronic presentation including memory decline, sleep disorder, bulbar symptoms and movement disorder. Post-mortem brains of patients with anti-IgLON5 disease show neurodegeneration with tau deposition sparking interest in this ‘acquired tauopathy’ as a disease model for neurodegeneration, yet mechanisms of neurodegeneration remain unknown. Using a reductionist human iPSC-derived neuron-antibody model, we applied proteomics approach, electrophysiology and live cell imaging. iNeurons treated with anti-IgLON5 IgG presented with cytoskeletal disruption along with tau depositions, which correlated with endophenotypes. Accompanying calcium dysregulation was driven by impaired ER refill and mitochondrial dysfunction leading to cell death. Analogous cytoskeletal disruption is also reflected in the serum of treatment naïve patients using OLink proteomics. These findings provide insight into anti-IgLON5 disease pathology and pinpoint downstream signalling events of direct antibody-neuron interactions, which involve novel targets such as cytoskeletal disruption along with calcium dysregulation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"86 ","pages":"Article 103854"},"PeriodicalIF":11.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}