Redox Biology最新文献

{"title":"Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure","authors":"Le Pan ,&nbsp;Chenxing Huang ,&nbsp;Xuejuan Jin ,&nbsp;Jian Wu ,&nbsp;Kejia Jin ,&nbsp;Jingyi Lin ,&nbsp;Ying Wang ,&nbsp;Jianxuan Li ,&nbsp;Chao Yin ,&nbsp;Xiang Wang ,&nbsp;Lei Zhang ,&nbsp;Guoping Zhang ,&nbsp;Hangming Dong ,&nbsp;Junli Guo ,&nbsp;Issei Komuro ,&nbsp;Yuxiang Dai ,&nbsp;Yunzeng Zou ,&nbsp;Hui Gong","doi":"10.1016/j.redox.2024.103466","DOIUrl":"10.1016/j.redox.2024.103466","url":null,"abstract":"<div><div>Sustained myocardial hypertrophy or left ventricular hypertrophy (LVH) triggered by pressure overload is strongly linked to adverse cardiovascular outcomes. Here, we investigated the clinical relationship between serum HSP90α (an isoform of HSP90) levels and LVH in patients with hypertension or aortic stenosis (AS) and explored underlying mechanisms in pressure overload mouse model. We built a pressure overload mouse model via transverse aortic constriction (TAC). Compared to controls, elevated <strong>s</strong>erum HSP90α levels were observed in patients with hypertension or AS, and the levels positively correlated with LVH. Similarly, HSP90α levels increased in heart tissues from patients with obstructive hypertrophic cardiomyopathy (HCM), and in mice post-TAC. TAC induced the enhanced cardiac expression and secretion of HSP90α from cardiomyocytes and cardiac fibroblasts. Knockdown of HSP90α or blockade of extracellular HSP90α (eHSP90α) attenuated cardiac hypertrophy and dysfunction by inhibition of β-catenin/TCF7 signaling under pressure overload. Further analysis revealed that eHSP90α interacted with EC1-EC2 region of N-cadherin to activate β-catenin, enhancing the transcription of hypertrophic genes by TCF7, resulting in cardiac hypertrophy and dysfunction under pressure overload. These insights suggest the therapeutic potential of targeting HSP90α-initiated signaling pathway against cardiac hypertrophy and heart failure under pressure overload.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103466"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning and SHAP value interpretation for predicting comorbidity of cardiovascular disease and cancer with dietary antioxidants","authors":"Xiangjun Qi ,&nbsp;Shujing Wang ,&nbsp;Caishan Fang ,&nbsp;Jie Jia ,&nbsp;Lizhu Lin ,&nbsp;Tianhui Yuan","doi":"10.1016/j.redox.2024.103470","DOIUrl":"10.1016/j.redox.2024.103470","url":null,"abstract":"<div><h3>Objective</h3><div>To develop and validate a machine learning model incorporating dietary antioxidants to predict cardiovascular disease (CVD)-cancer comorbidity and to elucidate the role of antioxidants in disease prediction.</div></div><div><h3>Methods</h3><div>Data were sourced from the National Health and Nutrition Examination Survey. Antioxidants, including vitamins, minerals, and polyphenols, were selected as key features. Additionally, demographic, lifestyle, and health condition features were incorporated to improve model accuracy. Feature preprocessing included removing collinear features, addressing class imbalance, and normalizing data. Models constructed within the mlr3 framework included recursive partitioning and regression trees, random forest, kernel k-nearest neighbors, naïve bayes, and light gradient boosting machine (LightGBM). Benchmarking provided a systematic approach to evaluating and comparing model performance. SHapley Additive exPlanation (SHAP) values were calculated to determine the prediction role of each feature in the model with the highest predictive performance.</div></div><div><h3>Results</h3><div>This analysis included 10,064 participants, with 353 identified as having comorbid CVD and cancer. After excluding collinear features, the machine learning model retained 29 dietary antioxidant features and 9 baseline features. LightGBM achieved the highest predictive accuracy at 87.9 %, a classification error rate of 12.1 %, and the top area under the receiver operating characteristic curve (0.951) and the precision‐recall curve (0.930). LightGBM also demonstrated balanced sensitivity and specificity, both close to 88 %. SHAP analysis indicated that naringenin, magnesium, theaflavin, kaempferol, hesperetin, selenium, malvidin, and vitamin C were the most influential contributors.</div></div><div><h3>Conclusion</h3><div>LightGBM exhibited the best performance for predicting CVD-cancer comorbidity. SHAP values highlighted the importance of antioxidants, with naringenin and magnesium emerging as primary factors in this model.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103470"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice","authors":"Linlin Zhang ,&nbsp;Fangshi Zhao ,&nbsp;Yize Li ,&nbsp;Zhenhua Song ,&nbsp;Lingyue Hu ,&nbsp;Yuanjie Li ,&nbsp;Rui Zhang ,&nbsp;Yonghao Yu ,&nbsp;Guolin Wang ,&nbsp;Chunyan Wang","doi":"10.1016/j.redox.2024.103472","DOIUrl":"10.1016/j.redox.2024.103472","url":null,"abstract":"<div><div>Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2 %) inhalation and hydrogen-rich saline (5 mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents <em>in vit</em>ro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103472"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen sulfide attenuates disturbed flow-induced vascular remodeling by inhibiting LDHB-mediated autophagic flux","authors":"Xia Wang ,&nbsp;Xiying Huang ,&nbsp;Yongya Zhang ,&nbsp;Huanhuan Huo ,&nbsp;Guo Zhou ,&nbsp;Linghong Shen ,&nbsp;Long Li ,&nbsp;Ben He","doi":"10.1016/j.redox.2024.103456","DOIUrl":"10.1016/j.redox.2024.103456","url":null,"abstract":"<div><div>Disturbed flow (DF) plays a critical role in the development and progression of cardiovascular disease (CVD). Hydrogen sulfide (H₂S) is involved in physiological processes within the cardiovascular system. However, its specific contribution to DF-induced vascular remodeling remains unclear. Here, we showed that the H₂S donor, NaHS suppressed DF-induced vascular remodeling in mice. Further experiments demonstrated that NaHS inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF), as well as the autophagy triggered by DF and PDGF. Mechanistically, RNA-Seq results revealed that NaHS counteracted the PDGF-induced upregulation of lactate dehydrogenase B (LDHB). Overexpression of LDHB abolished the protective effect of NaHS on DF-induced vascular remodeling. Furthermore, LDHB interacted with vacuolar-type proton ATPase catalytic subunit A (ATP6V1A), leading to lysosomal acidification, a process that was attenuated by NaHS treatment. The residues of leucine (Leu) 57 in ATP6V1A and serine (Ser) 269 in LDHB are critical for their interaction. Notably, the expression of LDHB was found to be elevated in vascular tissues from patients with abdominal aortic aneurysms (AAA) and thoracic aortic aneurysms (TAA). These data identify a molecular mechanism by which H₂S attenuates DF-induced vascular remodeling by inhibiting LDHB and disrupting the interaction between LDHB and ATP6V1A, thereby impeding the autophagy process. Our findings provide insight that H₂S or targeting LDHB has therapeutic potential for preventing and treating vascular remodeling.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103456"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial metabolism and redox signaling","authors":"Annika Müller-Eigner,&nbsp;Andrew P. Wojtovich","doi":"10.1016/j.redox.2024.103448","DOIUrl":"10.1016/j.redox.2024.103448","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103448"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Hydroxyisobutyric acid targeted binding to MT-ND3 boosts mitochondrial respiratory chain homeostasis in hippocampus to rescue diabetic cognitive impairment","authors":"Minzhen Xie ,&nbsp;Siqi Gu ,&nbsp;Yan Liu ,&nbsp;Haolin Yang ,&nbsp;Yuqi Wang ,&nbsp;Wei Yin ,&nbsp;Yang Hong ,&nbsp;Wanying Lu ,&nbsp;Chengbing He ,&nbsp;Lin Li ,&nbsp;Limin Zhao ,&nbsp;Jianjia Zhang ,&nbsp;Heng Liu ,&nbsp;Tian Lan ,&nbsp;Shuijie Li ,&nbsp;Qi Wang","doi":"10.1016/j.redox.2024.103446","DOIUrl":"10.1016/j.redox.2024.103446","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of diabetic cognitive impairment (DCI) is significant, some studies have shown that it is related to mitochondrial respiratory chain homeostasis, but the specific mechanism is not clear. 2-hydroxyisobutyric acid (2-HIBA) is a novel short-chain fatty acid with potential applications in the treatment of metabolic diseases because it can regulate mitochondrial disorders. Our aim was to explore a novel mechanism of action for 2-HIBA in the treatment of DCI in mitochondrial respiratory chain homeostasis.</div></div><div><h3>Methods</h3><div>Metabolic substances and differentially active metabolic pathways in the serum of diseased mice were identified based on multi-omics analysis. The nanoLC-Obitrap-MS technology was utilized to detect the content of selected small molecules with differential metabolic activity in the hippocampus and mitochondria of mice to evaluate their permeability through the blood-brain barrier (BBB) and outer mitochondrial membrane. A combination of behavioral, proteomic, and molecular biology approaches was used to explore specific regulatory mechanisms and identify potential pharmacological targets. Additionally, using techniques such as protein thermal shift, drug affinity responsive target stability (DARTS), hydrolase stability, and surface plasmon resonance (SPR) experiments, we demonstrated the direct binding effects of small molecule metabolites with protein targets.</div></div><div><h3>Results</h3><div>2-HIBA was found to directly ameliorate cognitive dysfunction in db/db mice by penetrating the blood-brain barrier and reversing the decrease in the protein content of NADH dehydrogenase 3 (MT-ND3) in the hippocampus through direct binding to ND3. This action helps maintain the stability of NAD⁺/NADH and regulate the mitochondrial respiratory chain balance. Furthermore, a combined medication plant agonist of 2-HIBA can enhance the expression of MT-ND3, thereby improving cognitive dysfunction in mice.</div></div><div><h3>Conclusion</h3><div>MT-ND3 is a crucial target for improving diabetic cognitive dysfunction, and 2-HIBA can directly bind to the MT-ND3 protein to alleviate the functional impairment of the mitochondrial respiratory chain in mice to treat DCI.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103446"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases","authors":"Ana I. Rojo ,&nbsp;Brigitta Buttari ,&nbsp;Susana Cadenas ,&nbsp;Ana Rita Carlos ,&nbsp;Antonio Cuadrado ,&nbsp;Ana Sofia Falcão ,&nbsp;Manuela G. López ,&nbsp;Milen I. Georgiev ,&nbsp;Anna Grochot-Przeczek ,&nbsp;Sentiljana Gumeni ,&nbsp;José Jimenez-Villegas ,&nbsp;Jarosław Olav Horbanczuk ,&nbsp;Ozlen Konu ,&nbsp;Isabel Lastres-Becker ,&nbsp;Anna-Liisa Levonen ,&nbsp;Viktorija Maksimova ,&nbsp;Charalambos Michaeloudes ,&nbsp;Liliya V. Mihaylova ,&nbsp;Michel Edwar Mickael ,&nbsp;Irina Milisav ,&nbsp;Albena T. Dinkova-Kostova","doi":"10.1016/j.redox.2024.103464","DOIUrl":"10.1016/j.redox.2024.103464","url":null,"abstract":"<div><div>Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a <em>cis</em>-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103464"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2 lactylation drives cancer cell resistance to ferroptosis through enhancing GCLC-dependent glutathione synthesis","authors":"Kaifeng Niu ,&nbsp;Zixiang Chen ,&nbsp;Mengge Li ,&nbsp;Guannan Ma ,&nbsp;Yuchun Deng ,&nbsp;Ji Zhang ,&nbsp;Di Wei ,&nbsp;Jiaqi Wang ,&nbsp;Yongliang Zhao","doi":"10.1016/j.redox.2024.103479","DOIUrl":"10.1016/j.redox.2024.103479","url":null,"abstract":"<div><div>Lactate-mediated lactylation on target proteins is recently identified as the novel posttranslational modification with profound biological functions. RNA 5-methylcytosine (m⁵C) modification possesses dynamic and reversible nature, suggesting that activity of its methyltransferase NSUN2 is actively regulated. However, how NSUN2 activity is response to acidic condition in tumor microenvironment and then regulates cancer cell survival remain to be clarified. Here, we demonstrate that NSUN2 activity is enhanced by lactate-mediated lactylation at lysine 508, which then targets glutamate-cysteine ligase catalytic subunit (GCLC) mRNA to facilitates GCLC m⁵C formation and mRNA stabilization. The activated GCLC induces higher level of intracellular GSH accompanied by decreased lipid peroxidation and resistant phenotype to ferroptosis induction by doxorubicin (Dox) in gastric cancer cells. Specifically, the effect of NSUN2 lactylation-GCLC-GSH pathway is nearly lost when NSUN2 K508R or GCLC C-A mutant (five cytosine sites) was introduced into the cancer cells. We further identify the catalytic subunit N-α-acetyltransferase 10 (NAA10) as the lactytransferase of NSUN2, and lactate treatment substantially enhances their association and consequent NSUN2 activation. Taken together, our findings convincingly elucidate the signaling axis of NAA10-NSUN2-GCLC that potently antagonizes the ferroptosis under acidic condition, and therefore, targeting NSUN2 lactylation might be an effective strategy in improving the prognosis of cancer patients.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103479"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases","authors":"Yiying Bian ,&nbsp;Jize Dong ,&nbsp;Zhengsheng Zhou ,&nbsp;Hua Zhou ,&nbsp;Yuanyuan Xu ,&nbsp;Qiang Zhang ,&nbsp;Chengjie Chen ,&nbsp;Jingbo Pi","doi":"10.1016/j.redox.2024.103476","DOIUrl":"10.1016/j.redox.2024.103476","url":null,"abstract":"<div><div>Over 10% of the global population is at risk to kidney disorders. Nuclear factor erythroid-derived 2-related factor 2 (NRF2), a pivotal regulator of redox homeostasis, orchestrates antioxidant response that effectively counters oxidative stress and inflammatory response in a variety of acute pathophysiological conditions, including acute kidney injury (AKI) and early stage of renal toxicity. However, if persistently activated, NRF2-induced transcriptional cascade may disrupt normal cell signaling and contribute to numerous chronic pathogenic processes such as fibrosis. In this concise review, we assembled experimental evidence to reveal the cell- and pathophysiological condition-specific roles of NRF2 in renal chemical toxicity, AKI, and chronic kidney disease (CKD), all of which are closely associated with oxidative stress and inflammation. By incorporating pertinent research findings on NRF2 activators, we dissected the spatiotemporal roles of NRF2 in distinct nephrotoxic settings and kidney diseases. Herein, NRF2 exhibits diverse expression patterns and downstream gene profiles across distinct kidney regions and cell types, and during specific phases of nephropathic progression. These changes are directly or indirectly connected to altered antioxidant defense, damage repair, inflammatory response, regulated cell death and fibrogenesis, culminating ultimately in either protective or deleterious outcomes. The spatiotemporal and paradoxical characteristics of NRF2 in mitigating nephrotoxicity suggest that translational application of NRF2 activation strategy for prevention and interventions of kidney injury are unlikely to be straightforward – right timing and spatial precision must be taken into consideration.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103476"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms","authors":"Maria João da Costa Caiado ,&nbsp;Amalia M. Dolga ,&nbsp;Wilfred F.A. den Dunnen","doi":"10.1016/j.redox.2024.103478","DOIUrl":"10.1016/j.redox.2024.103478","url":null,"abstract":"<div><div>Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce. Thus, we explore the current findings relating to the relationship of parkinsonism proteinopathy (α-synuclein in PD, and tau in PSP/CBD) paralleled to a specific form of cell death, ferroptosis. Ferroptosis is characterised by iron-induced lipid peroxidation and several markers of this pathway have been identified to control intracellular iron fluctuations. However, in parkinsonism, these mechanisms are thought to become dysfunctional. Although both proteinopathies have been linked to ferroptosis, much less is known about ferroptotic cell death and tau in the context of PSP/CBD. Interestingly, clinical trials targeting iron have recently shown conflicting results which begs to question the complexity of the ferroptotic pathway and alludes to the need for exploring other ferroptosis-related machinery as possible therapeutic targets. Overall, we address the literature gap in parkinsonism proteinopathy and ferroptosis, and its relevance to understanding disease pathophysiology and aetiology.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103478"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}