Redox Biology最新文献_第6页

Quantitative mapping of methionine sensitivity to oxidation in the copper-bound PcuC chaperone 铜结合PcuC伴侣体中蛋氨酸对氧化敏感性的定量图谱

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-19 DOI: 10.1016/j.redox.2026.104037

Lionel Tarrago , Lise Molinelli , Maya Belghazi , Mathilde Tribout , David Lemaire , Pierre Legrand , Sandrine Grosse , David Pignol , Monique Sabaty , Thierry Tron , Pascal Arnoux

Copper is typically coordinated by histidine, cysteine, or methionine in proteins, and these residues are particularly sensitive to oxidation. However, it remains unclear whether copper-coordinating residues are more prone to oxidation than non-coordinating ones, and how their susceptibility changes between the apo and copper-bound states. The copper chaperone PcuC, important for cytochrome c oxidase assembly in bacteria, contains a canonical binding site composed of two histidines and two methionines (H51x_nM63 × ₂₂H86xM88), as well as a disordered C-terminal extension enriched in methionine and histidine. To quantify methionine oxidation sensitivity in both apo- and Cu-bound PcuC, we used a methionine-specific oxaziridine probe combined with mass spectrometry and compared labeling patterns to those generated by ¹⁸O-labeled hydrogen peroxide. We show that methionine residues display distinct oxidation sensitivities in the apoprotein, and that the oxaziridine reacts similarly to H₂¹⁸O₂. Importantly, this probe enables quantification of methionine oxidation independently of hydroxyl radicals generated by copper-driven Fenton chemistry, which lacks residue specificity. In the copper-bound form, Cu binding strongly alters methionine reactivity, with a marked increase in oxidation of the coordinating Met63 and Met88. Structural analysis revealed that two copper ions occupy the canonical site, while the C-terminal extension does not contribute to coordination. Comparison of structural features and oxidation values showed that methionine sensitivity correlates with solvent exposure in the folded domain, but with local positive charge in the disordered region. These findings demonstrate that copper coordination modulates methionine oxidation, and that oxaziridine-based probes provide powerful tools for mapping oxidation sensitivity in (metallo)proteins.

铜通常与蛋白质中的组氨酸、半胱氨酸或蛋氨酸配合，这些残基对氧化特别敏感。然而，尚不清楚铜配位残基是否比非配位残基更容易氧化，以及它们的敏感性在载脂蛋白和铜结合态之间如何变化。铜伴侣蛋白PcuC对细菌细胞色素c氧化酶的组装具有重要意义，它含有一个由两种组氨酸和两种蛋氨酸组成的典型结合位点（H51xnM63 × 22H86xM88），以及一个富含蛋氨酸和组氨酸的无序c端延伸。为了量化载脂蛋白和铜结合的PcuC中蛋氨酸氧化敏感性，我们使用了蛋氨酸特异性的杂氮吡啶探针结合质谱，并将标记模式与18o标记的过氧化氢产生的标记模式进行了比较。我们发现甲硫氨酸残基在载脂蛋白中表现出明显的氧化敏感性，并且氧杂嗪与H218O2反应相似。重要的是，该探针能够定量蛋氨酸氧化，而不依赖于铜驱动芬顿化学产生的羟基自由基，这种化学缺乏残留特异性。在铜结合的形式下，铜结合强烈地改变了蛋氨酸的反应性，配位的Met63和Met88的氧化显著增加。结构分析表明，两个铜离子占据规范位点，而c端延伸不利于配位。结构特征和氧化值的比较表明，蛋氨酸的敏感性在折叠区与溶剂暴露有关，而在无序区与局部正电荷有关。这些发现表明铜配位调节蛋氨酸氧化，并且基于恶氮吡啶的探针为绘制（金属）蛋白的氧化敏感性提供了强大的工具。

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引用次数: 0

p53 and fatty acids collaborate to trigger ferroptosis via the FBXO2-FABP5 axis in colorectal cancer 在结直肠癌中，p53和脂肪酸通过FBXO2-FABP5轴共同触发铁下垂

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-19 DOI: 10.1016/j.redox.2026.104043

Jing Tong , Tao Han , Jun Deng , Yu Gan , Ruiwen Ruan , Wei Zhao , Chen Xiong , Quan Liao , Shiqi Chen , Huitong Bu , Jianping Xiong , Xiang Zhou , Qian Hao

In colorectal cancer (CRC), p53 can either suppress or potentiate tumor sensitivity to ferroptosis under oxidative stress conditions. However, it remains to be elucidated how p53 differentially regulates ferroptosis, and whether it can initiate ferroptosis. Our findings reveal that p53 induces ferroptosis in the presence of abundant polyunsaturated fatty acids (PUFAs). FBXO2, which is encoded by a p53-inducible target gene, interacts with FABP5 and promotes the lysosomal degradation of FABP5 through chaperone-mediated autophagy. This results in a decrease in the levels of PUFAs, thereby increasing resistance to ferroptosis in CRC. Notably, the supplementation of arachidonic acid not only reverses p53-mediated ferroptosis resistance, but also coordinates with p53 to initiate ferroptosis independently of additional oxidative stress, effectively suppressing the growth of CRC cells both in vitro and in vivo. Altogether, our study uncovers that the availability of PUFAs is crucial for p53 to exert a pro-ferroptotic function in CRC.

在结直肠癌（CRC）中，p53可以抑制或增强氧化应激条件下肿瘤对铁下垂的敏感性。然而，p53如何差异调控铁下垂，以及它是否能引发铁下垂仍有待阐明。我们的研究结果表明，p53在存在丰富的多不饱和脂肪酸（PUFAs）的情况下诱导铁下垂。FBXO2由p53诱导的靶基因编码，与FABP5相互作用，通过伴侣蛋白介导的自噬促进FABP5的溶酶体降解。这导致PUFAs水平降低，从而增加CRC对铁下垂的抵抗力。值得注意的是，补充花生四烯酸不仅可以逆转p53介导的铁下垂抗性，还可以与p53协同启动铁下垂，而不需要额外的氧化应激，从而在体外和体内有效抑制CRC细胞的生长。总之，我们的研究发现，PUFAs的可用性对于p53在CRC中发挥促铁功能至关重要。

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引用次数: 0

Upregulated GBP2 exacerbates Parkinson's disease pathogenesis by impairing NIX-dependent mitophagy 上调GBP2通过损害nix依赖性线粒体自噬而加剧帕金森病的发病机制

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-17 DOI: 10.1016/j.redox.2026.104029

Wenqi Cui , Tianlu Wang , Juan Feng

Parkinson's disease (PD), characterized by dopaminergic neuron loss, still lacks disease-modifying therapies due to incompletely understood mechanisms. Guanylate-binding proteins (GBPs) are well-known immune regulators, but their roles in PD are largely unknown. In this study, we identify GBP2 as a critical driver of PD pathogenesis by impairing mitophagy. We found that GBP2 was significantly upregulated in the substantia nigra of PD patients, and in both MPTP-induced and A53T transgenic mouse models, as well as in MPP⁺-treated or A53T α-synuclein-overexpressing SH-SY5Y cells. Both in vivo and in vitro, genetic knockdown of GBP2 robustly alleviated the MPTP/MPP⁺-induced motor deficits, dopaminergic neuron loss, and apoptosis. Mechanistically, PD-related stress promotes GBP2 geranylgeranylation, driving its mitochondrial accumulation. At mitochondria, GBP2 directly binds the mitophagy receptor NIX via its large GTPase domain and targets it for ubiquitin-proteasomal degradation, thereby suppressing NIX-mediated mitophagy. Accordingly, GBP2 knockdown enhanced mitophagy, improved mitochondrial homeostasis, and protected against neuronal apoptosis. The neuroprotective effects of GBP2 knockdown were abolished by either pharmacological inhibition of mitophagy or genetic knockdown of NIX, indicating a linear pathway. Importantly, therapeutically targeting geranylgeranylation with GGTI298 significantly attenuated MPTP-induced neurotoxicity. Our study unveils a novel, druggable axis in PD pathogenesis where GBP2 disrupts mitochondrial quality control. Targeting GBP2 geranylgeranylation with GGTI298 presents a promising therapeutic strategy.

帕金森氏病（PD）以多巴胺能神经元丧失为特征，由于机制不完全了解，仍然缺乏疾病改善疗法。鸟苷结合蛋白（gbp）是众所周知的免疫调节因子，但其在帕金森病中的作用在很大程度上是未知的。在这项研究中，我们发现GBP2通过损害线粒体自噬而成为PD发病的关键驱动因素。我们发现，在PD患者的黑质、mptp诱导和A53T转基因小鼠模型以及MPP+处理或A53T α-突触核蛋白过表达的SH-SY5Y细胞中，GBP2均显著上调。在体内和体外实验中，基因敲低GBP2均可显著减轻MPTP/MPP+诱导的运动缺陷、多巴胺能神经元损失和细胞凋亡。从机制上讲，pd相关应激促进GBP2香叶酰化，推动其线粒体积累。在线粒体中，GBP2通过其较大的GTPase结构域直接结合线粒体自噬受体NIX，并将其靶向泛素-蛋白酶体降解，从而抑制NIX介导的线粒体自噬。因此，GBP2敲低可增强线粒体自噬，改善线粒体稳态，并防止神经元凋亡。GBP2敲低的神经保护作用通过药物抑制线粒体自噬或基因敲低NIX而被消除，表明其是线性途径。重要的是，使用GGTI298治疗靶向香叶酰香叶酰化可显著减轻mptp诱导的神经毒性。我们的研究揭示了PD发病机制中一个新的、可用药的轴，其中GBP2破坏线粒体质量控制。用GGTI298靶向GBP2香叶酰化是一种很有前景的治疗策略。

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引用次数: 0

Acetyl-CoA acyltransferase 2 palmitoylation drives liver fibrosis by inducing hepatic stellate cell ferroptosis 乙酰辅酶a酰基转移酶2棕榈酰化通过诱导肝星状细胞铁下垂驱动肝纤维化

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-17 DOI: 10.1016/j.redox.2026.104035

Jianxiong Han , Zhongkang Yan , Zhiran Sun , Wenyuan Dang , Bao Li , Shuangshuang Li , Xinru Lv , Lin Ni , Anyuan He , Pengying Gu , Feifei Wang , Lili Wang , Xingyuan Yang

Hepatic fibrosis is a major driver of mortality in metabolic dysfunction-associated steatotic liver disease (MASLD)—previously known as non-alcoholic fatty liver disease (NAFLD). While hepatic stellate cell (HSC) activation and myofibroblast accumulation are central to fibrogenesis, the regulatory mechanisms remain incompletely understood. Acetyl-CoA acyltransferase 2 (ACAA2), a pivotal enzyme in fatty acid oxidation, has been implicated in lipid metabolism but has not been investigated as a therapeutic target in MASLD. Here, we show that ACAA2 upregulation in HSCs exacerbates hepatic fibrosis by promoting ferroptosis-associated transcriptional programs, whereas ACAA2 inhibition attenuates both ferroptosis and fibrogenesis in preclinical models. Mechanistically, ACAA2 palmitoylation governs its subcellular localization and function, and blocking this modification suppresses HSC activation via AMPK pathway stimulation, thereby mitigating fibrosis. Our study establishes ACAA2 palmitoylation as a druggable node for antifibrotic therapy, offering novel insights into metabolic regulation of hepatic fibrosis.

肝纤维化是代谢功能障碍相关脂肪变性肝病（MASLD）（以前称为非酒精性脂肪性肝病（NAFLD））死亡率的主要驱动因素。虽然肝星状细胞（HSC）活化和肌成纤维细胞积累是纤维形成的核心，但其调控机制仍不完全清楚。乙酰辅酶a酰基转移酶2 （ACAA2）是脂肪酸氧化中的关键酶，与脂质代谢有关，但尚未作为MASLD的治疗靶点进行研究。在这里，我们发现hsc中ACAA2的上调通过促进铁下垂相关的转录程序而加剧肝纤维化，而在临床前模型中，ACAA2的抑制可以减轻铁下垂和纤维化。机制上，ACAA2棕榈酰化控制其亚细胞定位和功能，阻断这种修饰通过AMPK通路刺激抑制HSC激活，从而减轻纤维化。我们的研究建立了ACAA2棕榈酰化作为抗纤维化治疗的可药物节点，为肝纤维化的代谢调节提供了新的见解。

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引用次数: 0

Inhibition of SDE2 Promotes Autophagy-Dependent Ferroptosis in Multiple Myeloma 抑制SDE2促进多发性骨髓瘤自噬依赖性铁下垂

IF 11.4 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-17 DOI: 10.1016/j.redox.2026.104007

Liang Xia, Jing Bao, Xiao-wen Chen, Yu-Chen Zhao, Xiang Wang, Yu Zheng

引用次数: 0

Context-specific Angiogenin-mediated tRNA fragments (tDRs) biogenesis shapes the mitochondrial stress response 情境特异性血管生成素介导的tRNA片段（tDRs）生物发生影响线粒体应激反应。

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-16 DOI: 10.1016/j.redox.2026.104038

Shadi Al-Mesitef , Daisuke Ando , Tomoya Saigasaki , Yuki Sakaguchi , Shunya Akagi , Abdulrahman Mousa , Sherif Rashad , Kuniyasu Niizuma

Transfer RNA-derived small RNAs (tDRs) are emerging regulators of cellular stress response, yet their biogenesis and activities during mitochondrial dysfunction remain poorly understood. Here we profiled tDRs generated in HEK293T cells exposed to inhibitors of respiratory complexes I–V (rotenone, TTFA, antimycin A, KCN, oligomycin) or to arsenite and assessed the impact of CRISPR-mediated angiogenin (ANG) knockout, ANG over-expression and recombinant ANG supplementation on the stress response and tDRs production. tDR-seq revealed stress-specific, highly ordered tDR repertoires: rotenone and antimycin predominantly induced internal (i-tRF) and 3ʹ tRNA (tRF3) fragments, whereas arsenite induced anticodon-cleaved tRNA halves (tiRNAs). mito-tDRs were mostly internal fragments and antimycin induced the strongest mitochondrial tDRs expression. ANG deletion markedly impaired stress-induced tDR biogenesis and sensitized cells to antimycin and oligomycin stress, whereas its overexpression selectively enhanced tDR biogenesis and conferred protection against these mitochondrial stressor. Synthetic tDR mimics failed to rescue viability, implying that native modification patterns or cooperative tDR pools are required. tDR motif enrichment analysis identified YBX1-binding sites among antimycin-induced tDRs, and genetic perturbation of YBX1 phenocopied aspects of enhanced mitochondrial bioenergetics and stress resistance. Together, these findings demonstrate that context-specific, ANG-directed tDR biogenesis forms a crucial arm of the mitochondrial stress response.

转移rna衍生的小rna （tDRs）是细胞应激反应的新兴调节因子，但它们在线粒体功能障碍中的生物发生和活动尚不清楚。在这里，我们分析了暴露于呼吸复合物I-V抑制剂（鱼藤酮、TTFA、抗霉素A、KCN、寡霉素）或亚砷酸盐的HEK293T细胞中产生的tdr，并评估了crispr介导的血管生成素（ANG）敲除、ANG过表达和重组ANG补充对应激反应和tdr产生的影响。tDR-seq揭示了应激特异性，高度有序的tDR谱：鱼烯酮和抗霉素主要诱导内部（i-tRF）和3 - tRNA （tRF3）片段，而亚砷酸盐诱导抗密码子切割tRNA半（tirna）。线粒体tdr主要为内部片段，抗霉素诱导的线粒体tdr表达最强。ANG缺失显著损害应激诱导的tDR生物发生，并使细胞对抗霉素和寡霉素应激敏感，而其过表达选择性地增强tDR生物发生，并赋予对这些线粒体应激源的保护作用。合成tDR模拟物未能挽救生存能力，这意味着需要本地修改模式或合作tDR池。tDR基序富集分析在抗霉素诱导的tDR中发现了YBX1结合位点，YBX1的遗传扰动在表型方面增强了线粒体生物能量学和抗逆性。综上所述，这些发现表明，环境特异性、ang导向的tDR生物发生形成了线粒体应激反应的重要组成部分。

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引用次数: 0

A positive effect of selenoprotein on mammary gland: Selenoprotein P stabilizes tight junctions by reducing cell death through inflammation mitigation in mice 硒蛋白对乳腺的积极作用：硒蛋白P通过减轻小鼠炎症减少细胞死亡来稳定紧密连接

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-16 DOI: 10.1016/j.redox.2026.104036

Mengran Zhu, Tianchao Xu, Hongli Lv, Yuxi Zhang, Jilong Luo, Mengyao Guo

Lactational mastitis threatens maternal-infant health and animal husbandry efficiency, with traditional antibiotics limited by milk residues and bacterial resistance. Selenium (Se) regulates inflammation via selenoproteins, but its core effector in mammary inflammation remains unclear. This study investigates the role and mechanism of Se and selenoprotein P (SeP) in LPS-induced mastitis. Tissue pathology, inflammation, apoptosis, and tight junctions (TJs) are assessed via H&E staining, qPCR, Western blot, etc., in mice with varying Se diets (deficient, basal, enriched) subjected to LPS-induced mastitis, and in mouse mammary epithelial cells (MMECs) with SeP silencing or enrichment. Se deficiency exacerbates LPS-induced acinar atrophy, inflammation, NF-κB activation, and release of pro-inflammatory factors (IL-6, IL-1β, TNF-α), while Se enrichment alleviates these effects. SeP, highly expressed in lactating mammary tissue and upregulated by Se, mediates protection through three pathways: inhibiting NF-κB to reduce inflammation, regulating the BAX/BCL2 balance and RIPK1/RIPK3/MLKL pathway to suppress apoptosis and necroptosis, and stabilizing TJ proteins (ZO-1, Occludin, Claudin-1) to repair the blood-milk barrier. In summary, SeP is a core effector of Se in regulating mammary inflammatory injury, maintaining lactational mammary homeostasis via anti-inflammatory, anti-apoptotic, and barrier-protective effects, and provides a new target for mastitis management.

哺乳期乳腺炎威胁着母婴健康和畜牧业效率，传统的抗生素受到乳残留和细菌耐药性的限制。硒（Se）通过硒蛋白调节炎症，但其在乳腺炎症中的核心效应尚不清楚。本研究探讨硒和硒蛋白P （SeP）在脂多糖性乳腺炎中的作用及其机制。通过H&；E染色、qPCR、Western blot等方法，对不同硒饮食（缺硒、基础硒、富集硒）小鼠lps诱导的乳腺炎，以及SeP沉默或富集的小鼠乳腺上皮细胞（MMECs）进行组织病理学、炎症、细胞凋亡和紧密连接（TJs）的评估。硒缺乏加剧了脂多糖诱导的腺泡萎缩、炎症、NF-κB活化和促炎因子（IL-6、IL-1β、TNF-α）的释放，而硒富集则减轻了这些影响。SeP在泌乳乳腺组织中高表达，受Se上调，通过抑制NF-κB减轻炎症，调节BAX/BCL2平衡和RIPK1/RIPK3/MLKL通路抑制细胞凋亡和坏死，稳定TJ蛋白（ZO-1、Occludin、Claudin-1）修复血乳屏障等途径发挥保护作用。综上所述，SeP是硒通过抗炎、抗凋亡和屏障保护等作用调节乳腺炎症损伤，维持哺乳期乳腺稳态的核心效应物，为乳腺炎治疗提供了新的靶点。

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引用次数: 0

Methylation reader MBD2-mediated GPX4 transcriptional repression drives ovarian granulosa cell ferroptosis in PCOS 甲基化读取器mbd2介导的GPX4转录抑制驱动PCOS卵巢颗粒细胞铁下垂

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-15 DOI: 10.1016/j.redox.2026.104034

Zhengquan Zhu , Yihan Wang , Xinye Yu , Tingyu Wang , Yin Li , Ruizhe Wang , Haiyun Chen , Binjia Ruan , Wangsen Cao , Gaojian Tao , Yong Wang , Daojuan Wang

Arrested follicular development and anovulation are hallmarks of polycystic ovary syndrome (PCOS), in which granulosa cell (GC) ferroptosis is emerging as a potential contributor. However, its precise role and regulation remain largely unknown. Here, we identify a methyl-CpG-binding domain protein 2 (MBD2)-driven ferroptotic program as a central pathogenic mechanism in PCOS. In a dehydroepiandrosterone (DHEA)-induced PCOS mouse model, GCs exhibited marked ferroptotic alterations and transcriptional suppression of glutathione peroxidase 4 (GPX4), a key anti-ferroptotic enzyme. GC-specific Gpx4 knockout exacerbated ferroptosis, impaired follicular maturation, reduced corpora lutea formation, and aggravated PCOS pathology. GPX4 repression was associated with increased DNA methyltransferases (DNMTs), elevated DNA Methyl-reading protein MBD2 and hypermethylation of the Gpx4 promoter. Pharmacological inhibition of MBD2 with KCC-07, or DNMT blockade with 5-Azacytidine, restored GPX4 expression, reduced lipid peroxidation and GC ferroptosis, and alleviated ovarian dysfunction. Integrative ATAC-seq and RNA-seq analyses revealed enhanced Gpx4 promoter accessibility in PCOS ovaries, where MBD2, MAZ, HDAC3 and NCoR assembled into a repressive complex that was interrupted by KCC-07 treatment. Importantly, pharmacologic GPX4 inhibition with RSL3 or GC-specific Gpx4 deletion abrogated the protective effects of MBD2 inhibition, establishing GPX4 repression as the critical downstream effector. Collectively, these findings uncover an MBD2-driven epigenetic program that silences GPX4, triggers GC ferroptosis, and promotes PCOS pathogenesis. Targeting MBD2 to restore epigenetic control of ferroptosis offers a promising therapeutic strategy for PCOS.

卵泡发育受阻和不排卵是多囊卵巢综合征（PCOS）的标志，其中颗粒细胞（GC）铁下垂是一个潜在的贡献者。然而，它的确切作用和监管在很大程度上仍然未知。在这里，我们发现甲基cpg结合域蛋白2 （MBD2）驱动的铁致凋亡程序是PCOS的主要致病机制。在脱氢表雄酮（DHEA）诱导的PCOS小鼠模型中，GCs表现出明显的铁致改变和谷胱甘肽过氧化物酶4 （GPX4）的转录抑制，GPX4是一种关键的抗铁致凋亡酶。gc特异性Gpx4基因敲除加剧了铁下垂、卵泡成熟受损、黄体形成减少和多囊卵巢综合征病理加重。GPX4抑制与DNA甲基转移酶（dnmt）增加、DNA甲基读取蛋白MBD2升高和GPX4启动子的超甲基化有关。KCC-07药物抑制MBD2，或5-氮胞苷阻断DNMT，恢复GPX4表达，减少脂质过氧化和GC铁下垂，减轻卵巢功能障碍。综合ATAC-seq和RNA-seq分析显示，PCOS卵巢中Gpx4启动子的可及性增强，其中MBD2、MAZ、HDAC3和NCoR组装成一个抑制复合体，被KCC-07治疗中断。重要的是，RSL3或gc特异性GPX4缺失的药理学抑制GPX4消除了MBD2抑制的保护作用，确立了GPX4抑制是关键的下游效应。总的来说，这些发现揭示了mbd2驱动的表观遗传程序，该程序沉默GPX4，触发GC铁吊，并促进PCOS的发病机制。靶向MBD2恢复铁下垂的表观遗传控制是治疗PCOS的一种有前景的治疗策略。

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引用次数: 0

Trem1 regulates neutrophil metabolism and recruitment in lung ischemia-reperfusion injury Trem1在肺缺血再灌注损伤中调节中性粒细胞代谢和募集

IF 11.4 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-14 DOI: 10.1016/j.redox.2026.104026

Fengjing Yang, Song Tong, Junhao Wan, Yixing Li, Jiani Gao, Yan Sun, Xiangfu Sun, Huikang Fu, Wenzhuo Luo, Jiayang Xu, Ting Zhou, SOWE BABOU, Junqi Wu, Guangjian Zhang, Chang Chen, Sihua Wang

引用次数: 0

Smog, sugar, and synapses: Unraveling the PM2.5-insulin resistance-Alzheimer’s disease axis 烟雾、糖和突触：揭示pm2.5 -胰岛素抵抗-阿尔茨海默病轴

IF 11.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Biology

Pub Date : 2026-01-14 DOI: 10.1016/j.redox.2026.104031

Hsuan-Yu Huang , Yu-Yin Huang , Chia-Lin Wu , Wei-Chien Huang , Chih-Ho Lai

Chronic exposure to fine particulate matter (PM2.5) and insulin resistance (IR) are each linked to Alzheimer’s disease (AD), but IR has not been systematically positioned as a mechanistic conduit through which PM2.5 heightens AD vulnerability. Drawing on epidemiological, animal, and cellular studies, this review outlines converging pathways along a PM2.5-IR-AD axis: chronic neuroinflammation, oxidative stress and mitochondrial dysfunction, blood-brain barrier disruption, and impaired amyloid-β (Aβ) clearance. Across sections, study-specific limitations are comprehensively discussed. Positioning IR as a central node linking PM2.5 exposure to AD reframes air pollution as a modifiable metabolic-neurologic risk. Potential therapeutic and preventive avenues are also highlighted. Future work could prioritize longitudinal and interventional studies that directly interrogate the PM2.5-IR-AD triad and refine biomarkers to guide precision prevention.

慢性暴露于细颗粒物（PM2.5）和胰岛素抵抗（IR）都与阿尔茨海默病（AD）有关，但IR尚未被系统地定位为PM2.5增加AD易感性的机制管道。根据流行病学、动物和细胞研究，本综述概述了沿PM2.5-IR-AD轴的趋同途径：慢性神经炎症、氧化应激和线粒体功能障碍、血脑屏障破坏和淀粉样蛋白-β (a β)清除受损。在各个章节中，全面讨论了特定研究的局限性。将IR定位为PM2.5暴露与AD之间的中心节点，将空气污染重新定义为可改变的代谢神经风险。还强调了潜在的治疗和预防途径。未来的工作可以优先考虑直接询问PM2.5-IR-AD三元组的纵向和介入性研究，并完善生物标志物以指导精确预防。

引用次数: 0