The FEBS journal最新文献_第6页

Transcription-coupled repair: tangled up in convoluted repair. 转录偶联修复：在卷曲修复中纠缠。

The FEBS journal Pub Date : 2025-04-24 DOI: 10.1111/febs.70104

Diana A Llerena Schiffmacher, Yun Jin Pai, Alex Pines, Wim Vermeulen

{"title":"Transcription-coupled repair: tangled up in convoluted repair.","authors":"Diana A Llerena Schiffmacher, Yun Jin Pai, Alex Pines, Wim Vermeulen","doi":"10.1111/febs.70104","DOIUrl":"https://doi.org/10.1111/febs.70104","url":null,"abstract":"Significant progress has been made in understanding the mechanism of transcription-coupled nucleotide excision repair (TC-NER); however, numerous aspects remain elusive, including TC-NER regulation, lesion-specific and cell type-specific complex composition, structural insights, and lesion removal dynamics in living cells. This review summarizes and discusses recent advancements in TC-NER, focusing on newly identified interactors, mechanistic insights from cryo-electron microscopy (Cryo-EM) studies and live cell imaging, and the contribution of post-translational modifications (PTMs), such as ubiquitin, in regulating TC-NER. Furthermore, we elaborate on the consequences of TC-NER deficiencies and address the role of accumulated damage and persistent lesion-stalled RNA polymerase II (Pol II) as major drivers of the disease phenotype of Cockayne syndrome (CS) and its related disorders. In this context, we also discuss the severe effects of transcription-blocking lesions (TBLs) on neurons, highlighting their susceptibility to damage. Lastly, we explore the potential of investigating three-dimensional (3D) chromatin structure and phase separation to uncover further insights into this essential DNA repair pathway.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucose sensing and the unfolded protein response. 葡萄糖传感和未折叠蛋白反应。

The FEBS journal Pub Date : 2025-04-24 DOI: 10.1111/febs.70113

Mabel Cruz-Rodríguez, Eric Chevet, Cristina Muñoz-Pinedo

{"title":"Glucose sensing and the unfolded protein response.","authors":"Mabel Cruz-Rodríguez, Eric Chevet, Cristina Muñoz-Pinedo","doi":"10.1111/febs.70113","DOIUrl":"https://doi.org/10.1111/febs.70113","url":null,"abstract":"The unfolded protein response (UPR) is activated primarily upon alteration of protein folding in the endoplasmic reticulum (ER). This occurs under physiological situations that cause an abrupt increase in protein synthesis, or under redox and metabolic stresses. Among the latter, hyperglycemia and glucose scarcity have been identified as major modulators of UPR signaling. Indeed, the first mammalian UPR effector, the glucose-regulated protein 78, also known as BiP, was identified in response to glucose deprivation. Tunicamycin, arguably the most commonly used drug to induce ER stress responses in vitro and in vivo, is an inhibitor of N-glycosylation. We compile here evidence that the UPR is activated upon physiological and pathological conditions that alter glucose levels and that this is mostly mediated by alterations of protein N-glycosylation, ATP levels, or redox balance. The three branches of the UPR transduced by PERK/ATF4, IRE1/XBP1s, and ATF6, as well as non-canonical ER sensors such as SCAP/SREBP, sense ER protein glycosylation status driven by glucose and other glucose-derived metabolites. The outcomes of UPR activation range from restoring protein N-glycosylation and protein folding flux to stimulating autophagy, organelle recycling, and mitochondrial respiration, and in some cases, cell death. Anabolic responses to glucose levels are also stimulated by glucose through components of the UPR. Therefore, the UPR should be further studied as a potential biomarker and mediator of glucose-associated diseases.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tracing the evolutionary pathway: on the origin of mitochondria and eukaryogenesis. 追踪进化途径：关于线粒体和真核发生的起源。

The FEBS journal Pub Date : 2025-04-24 DOI: 10.1111/febs.70109

J Ernesto Bravo-Arévalo

{"title":"Tracing the evolutionary pathway: on the origin of mitochondria and eukaryogenesis.","authors":"J Ernesto Bravo-Arévalo","doi":"10.1111/febs.70109","DOIUrl":"https://doi.org/10.1111/febs.70109","url":null,"abstract":"The mito-early hypothesis posits that mitochondrial integration was a key driver in the evolution of defining eukaryotic characteristics (DECs). Building on previous work that identified endosymbiotic selective pressures as central to eukaryotic cell evolution, this study examines how endosymbiotic gene transfer (EGT) and the resulting genomic and bioenergetic constraints shaped mitochondrial protein import systems. These systems were crucial for maintaining cellular function in early eukaryotes and facilitated their subsequent diversification. A primary focus is the co-evolution of mitochondrial import mechanisms and eukaryotic endomembrane complexity. Specifically, I investigate how the necessity for nuclear-encoded mitochondrial protein import drove the adaptation of bacterial secretion components, alongside eukaryotic innovations, to refine translocation pathways. Beyond enabling bioenergetic expansion, mitochondrial endosymbiosis played a fundamental role in the emergence of compartmentalisation and cellular complexity in LECA, driving the evolution of organellar networks. By integrating genomic, structural and phylogenetic evidence, this study aimed to contribute to the mito-early framework, clarifying the mechanisms that linked mitochondrial acquisition to the origin of eukaryotic cells.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRS85 and LEM3 suppressor mutations rescue stress hypersensitivities caused by lack of structural diversity of complex sphingolipids in budding yeast. TRS85和LEM3抑制基因突变可挽救出芽酵母因复杂鞘脂结构多样性缺乏而引起的应激超敏反应。

The FEBS journal Pub Date : 2025-04-23 DOI: 10.1111/febs.70094

Momoko Matsuzaki, Ayano Koga, Satomi Yamagata, Takahiro Kawaguchi, Motohiro Tani

{"title":"TRS85 and LEM3 suppressor mutations rescue stress hypersensitivities caused by lack of structural diversity of complex sphingolipids in budding yeast.","authors":"Momoko Matsuzaki, Ayano Koga, Satomi Yamagata, Takahiro Kawaguchi, Motohiro Tani","doi":"10.1111/febs.70094","DOIUrl":"https://doi.org/10.1111/febs.70094","url":null,"abstract":"The budding yeast Saccharomyces cerevisiae can synthesise 15 subtypes of complex sphingolipids, and this structural diversity is thought to be the molecular basis that enables the range of biological functions of complex sphingolipids. Through analyses of yeast mutants with various deletion combinations of complex-sphingolipid-metabolising enzyme genes (CSG1, CSH1, IPT1, SUR2 and SCS7), it was previously shown that less structural diversity of complex sphingolipids leads to increased sensitivity to multiple environmental stresses, with impaired plasma-membrane and cell-wall integrity. In this study, we screened for suppressor mutations that can alleviate the stress hypersensitivities of csg1Δ csh1Δ sur2Δ scs7Δ (ccssΔ) cells. Mutations of trafficking protein particle complex III-specific subunit 85 (TRS85; encodes a component of the TRAPPIII complex, involved in membrane trafficking) and phospholipid-transporting ATPase Dnf2 (DNF2; encodes the plasma-membrane glycerophospholipid flippase) were identified as suppressor mutations. Loss of Trs85 or phospholipid-transporting ATPase accessory subunit Lem3 (LEM3; encodes a regulatory subunit of Dnf2) differed in the type of stress being conferred resistance to ccss∆ cells. Furthermore, it was also found that impaired plasma-membrane and cell-wall integrities in ccssΔ cells were suppressed by trs85∆ but not lem3∆. Moreover, ccss∆ cells exhibited abnormal localisation of yeGFP-Snc1 in endosomes, which is suppressed by trs85∆ but not lem3∆. Overexpression of GTP-binding protein Ypt1, which is regulated by TRAPPIII and involved in vesicular trafficking, exacerbated plasma-membrane integrity abnormalities and stress sensitivities in ccss∆ cells. Thus, it was suggested that TRS85 and LEM3 deletion confer stress tolerances to ccssΔ cells through distinct mechanisms. These findings will provide insights into the physiological significance of the structural diversity of complex sphingolipids.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxaliplatin accelerates immunogenic cell death by activating the cGAS/STING/TBK1/IRF5 pathway in gastric cancer. 奥沙利铂通过激活胃癌中cGAS/STING/TBK1/IRF5通路加速免疫原性细胞死亡。

The FEBS journal Pub Date : 2025-04-22 DOI: 10.1111/febs.70102

Siwei Zhao, Dong Sun, Hang Yu, Menglin Wang, Botao Xu, Yufei Wang, Fangqi Hu, Xiaofeng Wang, Jiazi Zhang, Yongsheng Wang, Jie Chai

{"title":"Oxaliplatin accelerates immunogenic cell death by activating the cGAS/STING/TBK1/IRF5 pathway in gastric cancer.","authors":"Siwei Zhao, Dong Sun, Hang Yu, Menglin Wang, Botao Xu, Yufei Wang, Fangqi Hu, Xiaofeng Wang, Jiazi Zhang, Yongsheng Wang, Jie Chai","doi":"10.1111/febs.70102","DOIUrl":"https://doi.org/10.1111/febs.70102","url":null,"abstract":"Immunogenic cell death is a tumor cell death involving both innate and adaptive immune responses. Given the published findings that oxaliplatin causes the secretion of high mobility group box 1 (HMGB1) from cancer cells, which is necessary for the initiation of immunogenic cell death, we investigated whether oxaliplatin plays an anticancer role in gastric cancer by inducing immunogenic cell death and further explored its mechanism. We found that oxaliplatin inhibited viability and induced pyroptosis, immunogenic cell death, the production of reactive oxygen species, mitochondrial permeability transition pore (mPTP) opening, and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis activation in gastric cancer cells. Suppressing mPTP opening (cyclosporine treatment), depleting mitochondrial DNA (mtDNA; ethidium bromide treatment), or STING downregulation (H151 or si-STING treatment) reversed cGAS/STING pathway activation and the increased immunogenic cell death induced by oxaliplatin in MKN-45 and AGS cells. Moreover, oxaliplatin induced immunogenic cell death via activating the cGAS/STING/TANK-binding kinase 1 (TBK1; also known as serine/threonine-protein kinase TBK1)/interferon regulatory factor 5 (IRF5) pathway. In conclusion, oxaliplatin treatment could induce immunogenic cell death and mPTP opening and activate the cGAS/STING/TBK1/IRF5 pathway in gastric cancer cells.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Measuring catalytic mechanism similarity - a new approach to study enzyme function and evolution. 测定催化机理相似性——研究酶功能和进化的新途径。

The FEBS journal Pub Date : 2025-04-22 DOI: 10.1111/febs.70106

Antonio J M Ribeiro, Ioannis G Riziotis, Neera Borkakoti, Pedro A Fernandes, Maria J Ramos, Janet M Thornton

{"title":"Measuring catalytic mechanism similarity - a new approach to study enzyme function and evolution.","authors":"Antonio J M Ribeiro, Ioannis G Riziotis, Neera Borkakoti, Pedro A Fernandes, Maria J Ramos, Janet M Thornton","doi":"10.1111/febs.70106","DOIUrl":"https://doi.org/10.1111/febs.70106","url":null,"abstract":"Similarity measures for protein sequence, structure and enzyme reactions have been essential tools for translating an abundance of experimental data about enzymes into biological insights. Enzymes with similar sequence and structure, for example, can be organised into evolutionary families, and within families, reaction similarity can highlight examples of conservation or divergent evolution. When it comes to reaction mechanisms, despite their importance in explaining the catalytic power of enzymes and their evolution, no similarity measures have been developed until now. We addressed this gap by developing a method to calculate mechanism similarity based on the bond changes and charge transfers occurring at each catalytic step, where we have the ability to adjust the size of the chemical environment surrounding the atoms directly involved in these transformations. Using this newly developed method, we performed a pairwise comparison of all the mechanisms stored in the Mechanism and Catalytic Site Atlas (M-CSA) database. This analysis illustrates how mechanism similarity can be a powerful tool to navigate the known catalytic space and to discover and characterise both convergent and divergent evolutionary relationships.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New insights into Sti1/Hop's cochaperone function highlight the complexity of proteostatic regulation. 对Sti1/Hop的cochaperone功能的新见解强调了蛋白质抑制调节的复杂性。

The FEBS journal Pub Date : 2025-04-21 DOI: 10.1111/febs.70108

Gregory Lloyd Blatch, Adrienne Lesley Edkins

引用次数: 0

Structural and functional insights into extreme thermal stability and activity of two GH12 domains of a multidomain glycosidase from a hyperthermophilic euryarchaeon. 超嗜热euryarchaeon的多结构域糖苷酶的两个GH12结构域的极端热稳定性和活性的结构和功能见解。

The FEBS journal Pub Date : 2025-04-21 DOI: 10.1111/febs.70095

Kseniya S Zayulina, Evgenii N Frolov, Christina Stracke, Alexandra A Klyukina, Anna N Khusnutdinova, Peter Stogios, Tatiana Skarina, Alexander F Yakunin, Peter N Golyshin, Bettina Siebers, Tatiana E Shugaeva, Ilya V Kublanov

{"title":"Structural and functional insights into extreme thermal stability and activity of two GH12 domains of a multidomain glycosidase from a hyperthermophilic euryarchaeon.","authors":"Kseniya S Zayulina, Evgenii N Frolov, Christina Stracke, Alexandra A Klyukina, Anna N Khusnutdinova, Peter Stogios, Tatiana Skarina, Alexander F Yakunin, Peter N Golyshin, Bettina Siebers, Tatiana E Shugaeva, Ilya V Kublanov","doi":"10.1111/febs.70095","DOIUrl":"https://doi.org/10.1111/febs.70095","url":null,"abstract":"Bacteria and fungi are well known for efficient degradation of plant polysaccharides thanks to various enzymes involved in plant cell wall decomposition. However, little is known about the role of archaea in this process or the repertoire and features of their polysaccharide-degrading enzymes. In our previous work, we discovered an archaeal multidomain glycosidase (MDG) composed of three catalytic domains (GH5 and two GH12) and two cellulose-binding modules (CBM2). The recombinant MDG and individual GH5 catalytic domain were active against cellulose and a number of other polysaccharides at a wide range of temperatures, with optimum temperatures (Topt) of 60 °C and 80 °C, respectively. The present study was focused on the characterization of two GH12 domains of the MDG. Purified recombinant TMDG_GH12-1 and TMDG_GH12-2 proteins were active as individual enzymes but exhibited distinct catalytic properties. Both enzymes were thermostable and active at extremely high temperatures: TMDG_GH12-1 was active at 40-130 °C (Topt 100 °C), and its half-life (t½) at 100 °C was 42 h, which makes it one of the most thermostable glycosidases known so far, whereas TMDG_GH12-2 was active at 50-100 °C (Topt 90 °C) with t½ at 100 °C being 30 min. Phylogenetic and structural analysis of both TMDG_GH12 proteins together with molecular docking and site-directed mutagenesis suggested that the presence of two disulfide bridges and the W → Q mutation in the active site contribute to the exceptional thermostability of TMDG_GH12-1. Further structural and mutational studies of the TMDG_GH12-1 domain will help to gain a better understanding of the molecular mechanisms of its extraordinary thermostability and substrate specificity.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The small GTPase Rap1A expedites the NOX2 oxidative burst by facilitating Rac and NOX2 autoactivations. 小的GTPase Rap1A通过促进Rac和NOX2的自激活来加速NOX2的氧化爆发。

The FEBS journal Pub Date : 2025-04-21 DOI: 10.1111/febs.70107

Hope Elizabeth Johnson, Hope Gloria Umutesi, Jongyun Heo

{"title":"The small GTPase Rap1A expedites the NOX2 oxidative burst by facilitating Rac and NOX2 autoactivations.","authors":"Hope Elizabeth Johnson, Hope Gloria Umutesi, Jongyun Heo","doi":"10.1111/febs.70107","DOIUrl":"https://doi.org/10.1111/febs.70107","url":null,"abstract":"Rac and Rap1A are small GTPases with the redox-sensitive GX4GK(S/T)C/ECS and NKCD motif. Of the known NADPH oxidase (NOX) isoforms, NOX1 and NOX2 function with the redox-sensitive Rac. Both exhibit an oxidative burst in which superoxide production is initially lagged but then accelerated. This burst is a reflection of NOX1 and NOX2 autoactivations occurring alongside the redox-dependent Rac autoactivation. NOX2 also contains the redox-sensitive Rap1A. However, its role in NOX2 function was unknown. In this study, we show that Rap1A is also autoactivated by its redox response, which is coupled to Rac and NOX2 autoactivations. This coupling is found to be mediated through the Rap1A-dependent recruitment of the Rac GEF P-REX1 to the NOX2 system. We further show that the initiation threshold and propagation rate of Rap1A autoactivation are lower and slower, respectively, than those of Rac and NOX2. The low-threshold Rap1A autoactivation recruits P-REX1 to the NOX2 system, resulting in the production of active Rac, thereby aiding the high-threshold initiation and propagation of Rac and NOX2 autoactivations. This results in the rapid completion of the NOX2 oxidative burst, which is specific to NOX2 because NOX1 lacks Rap1A. The redox response differences between the Rap1A NKCD motif and the Rac GX4GK(S/T)C/ECS motif appear to be the basis for the feature differences between Rap1A autoactivation and those of Rac and NOX2 autoactivations. The GX4GK(S/T)C/ECS and NKCD motifs are found in many redox-sensitive Rho/Rab and Ras family GTPases, respectively. Findings here shed light on previously unknown redox-dependent functional distinctions between these small GTPases.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the impact of ferroptosis on diabetes-associated cognitive decline through comprehensive single-cell RNA sequencing and experimental studies. 通过全面的单细胞RNA测序和实验研究揭示铁下垂对糖尿病相关认知能力下降的影响。

The FEBS journal Pub Date : 2025-04-20 DOI: 10.1111/febs.70101

Yiping Zhang, Xiaolan Hu, Shoulin Chen, Fuzhou Hua, Zhenguo Zeng

{"title":"Unveiling the impact of ferroptosis on diabetes-associated cognitive decline through comprehensive single-cell RNA sequencing and experimental studies.","authors":"Yiping Zhang, Xiaolan Hu, Shoulin Chen, Fuzhou Hua, Zhenguo Zeng","doi":"10.1111/febs.70101","DOIUrl":"https://doi.org/10.1111/febs.70101","url":null,"abstract":"Diabetes-associated cognitive decline (DACD) is defined as an impairment of cognitive functions, including memory, attention and executive functions, attributed to chronic hyperglycemia and metabolic dysregulation associated with type 2 diabetes mellitus (T2DM). Ferroptosis is a regulated form of cell death that is dependent on iron and is primarily characterized by the excessive accumulation of lipid peroxides within cellular membranes, and also plays a critical role by exacerbating neuronal loss and synaptic dysfunction. The present study aims to use single-cell RNA sequencing (scRNA-seq) technology to investigate the role of ferroptosis in microglia and oligodendrocytes in DACD, thereby elucidating the pathogenesis of DACD. scRNA-seq and bulk RNA-seq datasets were analyzed for differential gene expression in hippocampus samples of T2DM and control mice, with an emphasis on oligodendrocytes and microglia cell types. We further constructed a T2DM model in mice and conducted behavioral analyses to evaluate cognitive functions. Additionally, we explored the role of ferroptosis in the progression of DACD disease by knocking down transferrin receptor 1 (Tfr1) using small interfering RNA and utilizing the ferroptosis inhibitor ferrostatin-1. The study identified significant alterations in the expression of ferroptosis-related genes Fth1, Slc40a1, Slc3a2, Trf, Tfrc and Sat1 in T2DM mice, suggesting the possible involvement of ferroptosis in DACD. Knocking down Tfr1 and inhibiting ferroptosis could significantly alleviate inflammation and oxidative stress damage in oligodendrocytes. This research provides new perspectives into the pathophysiology of DACD, emphasizing the critical role of ferroptosis and offering a potential therapeutic target to mitigate neurological damage and cognitive impairment associated with T2DM.","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0