Free Radical Biology and Medicine最新文献

{"title":"Corrigendum to \"Redox-dependent suppression of ATF3 impairs steroid sensitivity in asthma through MKP-1/p38 MAPK signaling\" [Free Radic. Biol. Med. 243 (2026) 1-15].","authors":"Jinxiu Li, Lei Zhao, Yali Qiu, Jiawei Liao, Xue Tian, Jianwei Gao, Min Zhang, Aihua Bao","doi":"10.1016/j.freeradbiomed.2026.04.149","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.04.149","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856137","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":"YOD1 Regulates Neuronal Mitochondrial Unfolded Protein Response Activation by Deubiquitinating DNAJA1 After Subarachnoid Hemorrhage.","authors":"Xi Liu, Bixi Gao, Lei Bai, Dengfeng Lu, Zhaoming Song, Zongqi Wang, Di Li, Chao Ma, Haiying Li, Zhong Wang","doi":"10.1016/j.freeradbiomed.2026.05.278","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.278","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction plays a critical role in early brain injury (EBI) following subarachnoid hemorrhage (SAH) and represents a promising therapeutic target.The mitochondrial unfolded protein response (UPR^mt) maintains mitochondrial homeostasis and enables neurons to cope with oxidative stress. In this study, we explored UPR^mt activation mediated by OTU-deubiquitinating enzyme 1 (YOD1) / DnaJ homolog subfamily A member 1 (DNAJA1) and its role in SAH.</p><p><strong>Methods: </strong>We isolated UPR^mt positive (UPR^mt+) and UPR^mt negative (UPR^mt-) primary neurons by flow cytometry and validated their differential tolerance to oxidative stress following SAH. We then explored the underlying causes of differential levels of UPR^mt activation. By combining molecular docking, co-immunoprecipitation, and protein stability assays, we established that YOD1 regulates the deubiquitination of DNAJA1. In addition, we assessed the neuroprotective role of YOD1 after SAH in vivo and in vitro models.</p><p><strong>Results: </strong>UPR^mt+ neurons exhibited reduced oxyhemoglobin (OxyHb)-induced apoptosis and mitochondrial damage compared with UPR^mt- neurons. DNAJA1 was upregulated and binding to HSP70 led to a strong activation of UPR^mt. DNAJA1 stability was regulated by the ubiquitin-proteasome system, and YOD1 stabilized DNAJA1 via deubiquitination. Neuron-specific YOD1 overexpression preserved mitochondrial function, reduced neuronal apoptosis in vitro and in vivo, and improved neurological outcomes in SAH.</p><p><strong>Conclusion: </strong>YOD1 stabilizes DNAJA1 through deubiquitination, promoting UPR^mt activation to mitigate mitochondrial dysfunction and neuronal death during EBI following SAH.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856029","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":"Ski promotes KLF4 expression to drive astrocyte senescence through the JAK2/STAT3 pathway after spinal cord injury in rats.","authors":"Yongqiang Shi, Kairong Song, Wenming Zhou, Yanbo Dong, Wei Song, Rui Ran, Guanghai Zhao, Kaisheng Zhou, Wei Nan, Haihong Zhang","doi":"10.1016/j.freeradbiomed.2026.04.152","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.04.152","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855663","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":"An integrated study of gut microbiota and serum metabolites in T2DM-ED rats after fecal microbiota transplantation.","authors":"Cheng Cheng, Lei Zheng, Xingjun Bao, Letian Wei, Hui Jiang, Tao Jiang","doi":"10.1016/j.freeradbiomed.2026.05.012","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.012","url":null,"abstract":"<p><p>Erectile dysfunction (ED) is a highly prevalent and refractory complication of type 2 diabetes mellitus (T2DM), with penile cavernosal dysfunction, inflammation, apoptosis, and fibrosis as core pathological features. Here we identify gut microbiota dysbiosis and its downstream metabolite arachidonic acid (AA) as critical mediators of T2DM-associated erectile dysfunction (T2DM-ED) through a systemic gut-penis axis. Gut dysbiosis is sufficient to induce an ED phenotype, as demonstrated by fecal microbiota transplantation (FMT) from T2DM-ED rats into pseudo-germ-free recipients, which successfully transferred the erectile impairment with significantly decreased ICP/MAP ratios. Recipient rats showed impaired colonic barrier integrity, mucosal damage, goblet cell depletion, and downregulated tight junction proteins (Occludin, Claudin-4). Multi-omics integration of 16S rRNA sequencing and serum metabolomics identified AA as a key elevated metabolite that drives inflammatory signaling via the HIF-1α and NF-κB pathways. In penile corpus cavernosum tissue, ED-FMT rats displayed smooth muscle loss, fibrosis, increased apoptosis, and hyperactivation of the TLR4-MyD88-NF-κB-HIF-1α axis. In primary corpus cavernosum smooth muscle cells (CCSMCs), AA stimulation recapitulated pathological activation, including a pro-apoptotic shift in the Bax/Bcl-2 ratio, elevated Cleaved Caspase-3, reduced α-SMA, increased COX-2, stabilized HIF-1α, and excessive PGE₂ production; these effects were abolished by pharmacological inhibition of NF-κB. Mechanistically, gut dysbiosis-induced systemic AA accumulation triggers inflammatory damage, apoptosis, and functional impairment in penile smooth muscle via the TLR4-MyD88-NF-κB/HIF-1α cascade. These findings define a gut-AA-NF-κB-penis axis that drives T2DM-ED pathogenesis, highlighting AA and its downstream signaling as promising therapeutic targets for diabetic erectile dysfunction.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856128","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":"Salubrinal-activated integrated stress response protects against doxorubicin-induced cardiotoxicity via activating transcription factor 4-mediated antioxidant defense and glutathione homeostasis.","authors":"Sheng-Fan Wang, Hsuan-Yu Chou, Pei-Hsun Liu, Hsing-Hui Su, Giun-Yi Hung, Chian-Ying Chou, Ling-Ming Tseng, Yuh-Chiang Shen, Jiin-Cherng Yen, Shiang-Suo Huang, Hsin-Chen Lee","doi":"10.1016/j.freeradbiomed.2026.05.281","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.281","url":null,"abstract":"<p><p>Doxorubicin is an effective chemotherapeutic agent; however, its use is limited by cardiotoxicity. Mitochondrial dysfunction is a central driver of doxorubicin-mediated cardiotoxicity. The role of the integrated stress response (ISR), a mitochondria-to-nucleus signaling pathway and crucial cellular defense mechanism in doxorubicin-induced cardiotoxicity, remains unclear. We investigated the pharmacological ISR activator salubrinal, a selective inhibitor of eukaryotic initiation factor 2α dephosphorylation with potential cardioprotective properties, to elucidate the molecular mechanisms underlying ISR-mediated cardioprotection in H9c2 cardiomyocytes, C57BL/6 mice, and HL-1 cell models. Doxorubicin disrupts ISR signaling, whereas salubrinal alleviates cardiotoxicity by activating transcription factor 4 (ATF4, a central ISR hub)-dependent pathways that suppress doxorubicin-induced apoptosis and preserve mitochondrial metabolism. The cystine/glutamate antiporter xCT, essential for glutathione (GSH) homeostasis, and growth differentiation factor 15 (GDF15), a mitochondrial stress-induced mitokine and potential biomarker of doxorubicin cardiotoxicity, are both regulated by ATF4. Mechanistically, we found that salubrinal contributes to cardioprotection against doxorubicin by enhancing the GSH-based antioxidant capacity via the ATF4-dependent GDF15-xCT axis. Further analysis of ATF4-associated GSH regulatory pathways revealed that enzymes involved in serine metabolism and glutathione peroxidase 4, a critical enzyme in GSH utilization that is upregulated by ATF4-mediated heat shock 70 kDa protein 5 and cystathionine gamma-lyase, contribute to the cardioprotective effects of salubrinal against doxorubicin-induced oxidative stress. Our findings highlight the ISR as a vital survival mechanism in cardiomyocytes exposed to doxorubicin. Regulating antioxidant defenses through enhanced GSH homeostasis and ISR activation, particularly via pharmacological agents such as salubrinal, may offer a promising therapeutic strategy for mitigating doxorubicin-induced cardiotoxicity.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856179","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":"Lysosomal function, resistance to oxidative stress and repair are compromised by expression of the Alexander disease GFAP R239C mutant.","authors":"Elena Hernández-Gerez, Nuria Goya-Iglesias, Álvaro Viedma-Poyatos, María A Pajares, Dolores Pérez-Sala","doi":"10.1016/j.freeradbiomed.2026.05.280","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.280","url":null,"abstract":"<p><p>Intermediate filaments are critical regulators of cell responses and organizers of cellular structures. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that provides structural and functional support to astrocytes. GFAP is a key target of oxidative stress and its expression and assembly are altered in brain disease and injury. Moreover, GFAP mutations can provoke protein aggregation and proteostasis defects, astrocytic damage and ultimately neurodegeneration causing the leukodystrophy known as Alexander disease (AxD). We previously showed mitochondrial alterations and oxidative stress in astrocytes expressing GFAP AxD mutants. Here, we address the impact of GFAP AxD mutants on the lysosomal degradation pathway, using an astrocytoma cell model. Lysosomes in cells expressing GFAP R239C, a variant associated with severe AxD, displayed abnormal distribution, defective activity and impaired intraluminal acidification. Lysosomes are primary sites of oxidative damage. Expression of GFAP R239C increased their susceptibility to oxidative stress, provoking a greater loss of lysosomal \"mass\" and compromised membrane integrity, revealed by increased intraluminal galectin recruitment, compared to cells expressing GFAP wt. Notably, lysosomes in GFAP R239C expressing cells were also more vulnerable to chemically-induced rupture. Interestingly, whereas lysosomes of cells expressing GFAP wt rapidly recovered after removal of the damaging agent, recovery of acidic vesicles was severely impaired in cells expressing GFAP R239C, suggesting a defect in lysosomal repair. Together, our results show that expression of the GFAP R239C AxD mutant is sufficient to deeply perturb lysosomal distribution, function and repair. These alterations could contribute to proteostasis defects and cellular toxicity in AxD.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856208","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":"Polystyrene nanoplastics drive neuronal senescence via PP2A-B56γ-targeted p-Ebp1^Ser335 dephosphorylation-mediated ribosome biogenesis dysfunction.","authors":"Yun-Lu Gao, Ming-Zhu Wang, Lei-Lei Wang, Ze-Bang Du, Yu-Han Xie, Wen-Qi Xu, Yu-Han Wang, Ruo-Han Li, Dong-Bei Guo, Han-Ying Zheng, You-Liang Yao, Ya-Bin Song, Zhong-Ning Lin, Yu-Chun Lin","doi":"10.1016/j.freeradbiomed.2026.05.016","DOIUrl":"10.1016/j.freeradbiomed.2026.05.016","url":null,"abstract":"<p><p>Nanoplastics (NPs) exhibit neurotoxicity, yet the precise molecular mechanisms remain elusive. In this study, we established a human-relevant polystyrene nanoplastics (PS-NPs, 50 mg kg^-1) oral exposure model in C57BL/6 mice in vivo and a neuro-immune microglial-neuron co-culture system (HMC-3/SH-SY5Y cells) in vitro to dissect these mechanisms. We demonstrate that PS-NPs exposure triggers microglial M1 activation and drives neuronal senescence. Mechanistically, PS-NPs activate the protein phosphatase 2A (PP2A)-B56γ subunit, which selectively dephosphorylates the ribosome biogenesis regulator ErbB3-binding protein 1 (Ebp1) at Ser335. This post-translational modification reduces Ebp1 nucleolar localization, suppresses 47S pre-ribosomal RNA transcription, and induces nucleolar stress. Consequently, the p53/p21 pathway is engaged, promoting neuronal senescence. Pharmacological inhibition of PP2A with LB-100 restored ribosome biogenesis, prevented neuronal senescence, and rescued cognitive deficits and neurodegenerative phenotypes in PS-NP-exposed mice. This is the first study to identify the PP2A-B56γ-p-Ebp1^Ser335-ribosome biogenesis axis as a novel cascade mechanism driving PS-NP-induced neuronal senescence. Our findings offer a targetable strategy to mitigate nanoplastics-associated neurodegeneration.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":"150-165"},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835662","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":"Metabolic energy expenditure in human blood long-lived neutrophils reprogrammed with inflammatory cytokines.","authors":"Yann Breton, Jules Gignac, Tân Khoa Lam, Christopher M Fortin, Helya Mortazavi, Isabelle Allaeys, Sylvain G Bourgoin, Patrice E Poubelle, Martin Pelletier","doi":"10.1016/j.freeradbiomed.2026.05.279","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.279","url":null,"abstract":"<p><p>The development of new analytical tools has revealed the heterogeneity of neutrophils in healthy and disease subjects. Knowledge of this heterogeneity has led to the identification, in healthy individuals, of a minor subset of blood neutrophils that express anti-protease genes characteristic of in vivo long-lived neutrophils, similar to those we previously described in vitro, which are expanded in autoimmune diseases. We can reprogram normal human blood neutrophils in vitro using GM-CSF, TNF, and IL-4, resulting in long-lived (LL) cells with enhanced glycolysis and oxygen consumption. We further report that these LL neutrophils express numerous genes associated with metabolism and mitochondria, including PLPP3 and SLC25A27. In addition, we confirmed that LL neutrophils express anti-peptidase genes, the most expressed being the PI3 gene, and secrete the peptidase inhibitor elafin and the secretory leukocyte protease inhibitor. Extracellular flux analysis revealed that PI3-expressing LL neutrophils exhibit enhanced glycolysis and respiration in response to pro-inflammatory cytokines, whereas non-reprogrammed neutrophils remain unresponsive. PI3-expressing LL neutrophils have a mitochondrial respiration partly driven by pyruvate oxidation, as demonstrated by the use of an inhibitor of mitochondrial pyruvate carrier. In contrast, oxygen consumption in control neutrophils was driven by fatty acid oxidation, as shown by the effect of inhibiting carnitine palmitoyltransferase 1. Thus, the reprogramming of neutrophils with GM-CSF, TNF, and IL-4 into cells capable of producing peptidase inhibitors is associated with an original metabolic phenotype characterized by active mitochondrial pathways.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835652","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":"TSPO Integrates Redox and Immune Homeostasis in Dermal Fibroblasts to Restrain Vitiligo Pathogenesis.","authors":"Jinpeng Lv, Chuanwei Yin, Wenhao Yu, Peiwen Jiang, Wenhui Xu, Huansha Zhang, Yan Cao, Rongyin Gao","doi":"10.1016/j.freeradbiomed.2026.05.009","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.009","url":null,"abstract":"<p><p>Vitiligo is a chronic depigmenting disorder characterized by oxidative stress-driven melanocyte loss and T cell-mediated immune activation. While melanocytes and keratinocytes have been extensively studied, the contribution of dermal fibroblasts to the oxidative and immune microenvironment remains unclear. Here, we identify the mitochondrial translocator protein (TSPO) as a key regulator of redox, inflammatory, and adhesion signaling in dermal fibroblasts. TSPO expression was markedly upregulated in both H₂O₂-treated fibroblasts and skin biopsies from vitiligo patients, suggesting a compensatory response to oxidative injury. TSPO deficiency aggravated mitochondrial dysfunction, lipid peroxidation, and apoptosis, while its overexpression restored mitochondrial potential, ATP production, and calcium homeostasis. Mechanistically, TSPO activated the p62/Keap1/Nrf2/HO-1 pathway to enhance antioxidant defense and concurrently suppressed NF-κB, NLRP3, and STAT1 signaling, reducing the expression of pro-inflammatory mediators and adhesion regulators. Pharmacological activation of TSPO with the high-affinity ligand Ro5-4864 restored mitochondrial function, reinforced antioxidant capacity, and alleviated depigmentation in an H₂O₂-induced vitiligo mouse model, while also diminishing CD8⁺ T cell infiltration and enhancing HO-1 expression. Our findings establish TSPO as a mitochondrial safeguard in dermal fibroblasts, integrating redox control and inflammatory restraint, and highlight TSPO ligands as promising therapeutics for vitiligo.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835743","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":"TRIM16 attenuates TDP43-mediated oxidative injury by coordinating Nrf2 activation and TFR1 autophagic degradation.","authors":"Qiuyu Chen, Yujun Zhou, Yuchen Peng, Jiaqi Lan, Yuying Kang, Lei Wu, Jiao Liu, Jingshu Tang, Ying Peng","doi":"10.1016/j.freeradbiomed.2026.05.014","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2026.05.014","url":null,"abstract":"<p><p>TAR DNA-binding protein 43 (TDP43) aggregation is a well-established pathological hallmark of amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders, contributing significantly to oxidative stress and neuronal injury. Here, we report that the M337V mutation in TDP43 exacerbates its proteotoxicity relative to the wild-type protein. Concurrently, multi-omics analysis revealed a pronounced downregulation of TRIM16 in motor neuron-like cells expressing either wild-type or M337V mutant TDP43. Functional studies demonstrated that TRIM16 overexpression effectively mitigated oxidative stress, restored mitochondrial integrity, and suppressed ferroptosis. Mechanistically, TRIM16 promoted the ubiquitination and degradation of Keap1, thereby facilitating the activation of Nrf2-mediated antioxidant genes. Furthermore, we identified the iron import receptor TFR1 as a novel ubiquitination substrate of TRIM16. TRIM16 mediated the ubiquitination of TFR1 and targeted it for p62-dependent autophagic degradation, which in turn reduced iron accumulation and lipid peroxidation. Collectively, our findings establish TRIM16 as a pivotal suppressor of TDP43-induced toxicity by orchestrating dual cytoprotective pathways to enhance cellular resilience, highlighting its promising therapeutic potential for TDP43 proteinopathy.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"252 ","pages":"132-149"},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835734","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}