Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 15

Опубликована: Авг. 24, 2022

Traumatic brain injury (TBI) is a serious health issue with high incidence, morbidity, and mortality that poses large burden on society. Further understanding of the pathophysiology cell death models induced by TBI may support targeted therapies for patients. Ferroptosis, model programmed first defined in 2012, characterized iron dyshomeostasis, lipid peroxidation, glutathione (GSH) depletion. Ferroptosis distinct from apoptosis, autophagy, pyroptosis, necroptosis has been shown to play role secondary worsen long-term outcomes after TBI. This review systematically describes (1) regulatory pathways ferroptosis TBI, (2) neurobiological links between other models, (3) potential targeting

Язык: Английский

---

Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

Virologica Sinica, Год журнала: 2023, Номер 39(1), С. 31 - 43

Опубликована: Сен. 9, 2023

Human endogenous retroviruses (HERVs) are remnants of retroviral infections in human germline cells from millions years ago. Among these, ERVW-1 (also known as HERV-W-ENV, ERVWE1, or ENVW) encodes the envelope protein HERV-W family, which contributes to pathophysiology schizophrenia. Additionally, neuropathological studies have revealed cell death and disruption iron homeostasis brains individuals with Here, our bioinformatics analysis showed that differentially expressed genes prefrontal cortex RNA microarray dataset (GSE53987) were mainly related ferroptosis its associated pathways. Clinical data demonstrated significantly lower expression levels ferroptosis-related genes, particularly Glutathione peroxidase 4 (GPX4) solute carrier family 3 member 2 (SLC3A2), schizophrenia patients compared normal controls. Further in-depth analyses a significant negative correlation between GPX4/SLC3A2 Studies indicated increased levels, malondialdehyde (MDA), transferrin receptor 1 (TFR1) while decreasing glutathione (GSH) triggering loss mitochondrial membrane potential, suggesting can induce ferroptosis. Ongoing research has shown reduced GPX4 SLC3A2 by inhibiting their promoter activities. Moreover, Ferrostatin-1 (Fer-1), inhibitor, reversed accumulation potential loss, well restored expressions markers GSH, MDA, TFR1 induced ERVW-1. In conclusion, could promote downregulating SLC3A2, revealing novel mechanism neuronal

Язык: Английский

---

Ketogenic diet alleviates brain iron deposition and cognitive dysfunction via Nrf2-mediated ferroptosis pathway in APP/PS1 mouse

Brain Research, Год журнала: 2023, Номер 1812, С. 148404 - 148404

Опубликована: Май 8, 2023

Язык: Английский

---

Iron‐associated lipid peroxidation in Alzheimer's disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(1)

Опубликована: Янв. 1, 2025

Abstract INTRODUCTION Iron‐mediated cell death (ferroptosis) is a proposed mechanism of Alzheimer's disease (AD) pathology. While iron essential for basic biological functions, its reactivity generates oxidants which contribute to damage and death. METHODS To further resolve mechanisms iron‐mediated toxicity in AD, we analyzed post mortem human brain ApoEFAD mice. RESULTS AD brains had decreased antioxidant enzymes, including those mediated by glutathione (GSH). Subcellular analyses showed greater oxidative lower enzymes lipid rafts, the site amyloid processing, than non‐raft membrane fraction. Apolipoprotein E ε4 carriers raft yield with oxidation. The hypothesized role pathology was tested mice chelation deferoxamine, fibrillar peroxidation, together increased GSH‐mediated antioxidants. DISCUSSION These novel molecular pathways highlight rafts during AD. Highlghts have numerous markers ferroptosis, reduced levels, storage. Lipid cases enzyme levels activity are most severe apolipoprotein carriers. Neuronal correlated defense, signaling proteins suggesting that neuronal loss linked these events. Chelation early‐onset familial model reduces peroxidation amyloid.

Язык: Английский

---

Bioinformatics identification of potential biomarkers and therapeutic targets for ischemic stroke and vascular dementia

Experimental Gerontology, Год журнала: 2024, Номер 187, С. 112374 - 112374

Опубликована: Фев. 6, 2024

Ischemic stroke and vascular dementia, as common cerebrovascular diseases, with the former causing irreversible neurological damage latter cognitive memory impairment, are closely related have long received widespread attention. Currently, potential causative genes of these two diseases yet to be investigated, effective early diagnostic tools for not emerged. In this study, we screened new biomarkers analyzed therapeutic targets both from perspective immune infiltration. Two gene expression profiles on ischemic dementia were obtained NCBI GEO database, key identified by LASSO regression SVM-RFE algorithms, GO KEGG enrichment. The CIBERSORT algorithm was applied profile species quantify 24 subpopulations cells. Moreover, logistic modeling analysis illustrate stability in diagnosis. Finally, validated using RT-PCR assay. A total 105 intersecting DEGs 2 sets datasets, bioinformatics functional showed that mainly involved purine ribonucleoside triphosphate metabolic process,respiratory chain complex,DNA−binding transcription factor binding active transmembrane transporter activity. is Oxidative phosphorylation, cAMP signaling pathway. finally three genes, GAS2L1, ARHGEF40 PFKFB3, prediction model determined GAS2L1 (AUC: 0.882), 0.867) PFKFB3 0.869), had good performance. Meanwhile, disease core infiltration related, highest positive correlation macrophage M1 (p < 0.001) negative mast cell activation = 0.0017); B cells naive 0.001), 0.0047). results relative mRNA levels ARHGEF40, significantly elevated populations groups 0.05). Immune infiltration-based models can used predict diagnosis patients provide a treatment diseases.

Язык: Английский

---

Repair and regeneration: ferroptosis in the process of remodeling and fibrosis in impaired organs

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Окт. 2, 2024

Язык: Английский

---

Identification and Validation of Biomarkers for Alzheimer’s Disease Based on Akt and Wnt Signaling Pathways in Mouse Models

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Alzheimer's disease (AD) is a neurodegenerative that remains challenging to treat. Akt and Wnt play role in complex cellular signaling, which crucial for examining the onset of AD. In this study, we aimed identify analyze pathway-related genes (ARGs) (WRGs) as AD biomarkers, determine effects ARGs WRGs on AD, verify these mouse models. We searched differentially expressed Gene Expression Omnibus database, constructed candidate gene protein–protein interaction networks, used least absolute shrinkage selection operator regression analysis support vector machine-recursive feature elimination algorithm screen key genes. Correlation functional similarity analyses genes, immune infiltration analysis, competing endogenous RNA network construction, drug prediction were performed. streptozotocin-treated (STZ)-treated mice was validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Bioinformatics identified five AD: PRKACA, CDH3, ATP6V0C, DLL1, CELSR2. Step-down tests, immunohistochemistry, silver plate staining confirmed successful treatment STZ-induced mice. According RT-qPCR relative expression DLL1 mRNA higher than control mice, whereas ATP6V0C PRKACA lower mice; consistent with results bioinformatics (p < 0.05). This study screened biomarkers associated pathways

Язык: Английский

---

Insights into growth retardation and dwarfism caused by goose parvovirus in goslings: a transcriptomic profiling study

Frontiers in Veterinary Science, Год журнала: 2025, Номер 12

Опубликована: Май 6, 2025

Goose parvovirus (GPV) poses a significant threat to the waterfowl industry as it results in high mortality rate and stunted growth surviving goslings, leading economic losses. We used 120 goslings goose embryo fibroblasts inoculated with GPV SYG61 strain study pathogenesis of by pathological gene expression profile changes. Fourteen days after infection strain, showed 63.33%, along dwarfism, weight loss, severe histopathological lesions liver jejunum. Serum analysis revealed marked increase levels immunosuppressive factors such TGF- β IL-10 ( p &lt; 0.01 or 0.05), while pro-inflammatory cytokines IL-4, IFN- γ , TNF- α IgG remained unaffected. In addition, inhibited proliferation induced apoptosis, demonstrated transcriptomic analysis, which identified 285 differentially expressed genes (DEGs). These DEGs were enriched pathways involved negative regulation cell (GO: 0008285, 19/276, LogP = −12.62) skeletal system development 0001501, 25/227, −12.51), key including IL6 CXCL8 PTGDS PI15 MMP9 MMP13 MMP2 CCN3 FAM180A . Other linked IL-17 signaling pathway (hsa04657) programmed death 0043068). Notably, activated both apoptosis ferroptosis through upregulation regulatory PTGS2 TF ASCL1 0.01). findings indicated that triggers inflammatory responses death, disturbs related development, causes retardation dwarfism infected goslings. This provides valuable insights into pathogenic mechanisms offers potential strategies mitigate its impact improve productivity industry.

Язык: Английский

---

Pb induces ferroptosis in choroid plexus epithelial cells via Fe metabolism

NeuroToxicology, Год журнала: 2023, Номер 95, С. 107 - 116

Опубликована: Янв. 13, 2023

Язык: Английский

---

Identification of the feature genes involved in cytokine release syndrome in COVID-19

PLoS ONE, Год журнала: 2024, Номер 19(1), С. e0296030 - e0296030

Опубликована: Янв. 2, 2024

Objective Screening of feature genes involved in cytokine release syndrome (CRS) from the coronavirus disease 19 (COVID-19). Methods The data sets related to COVID-19 were retrieved using Gene Expression Omnibus (GEO) database, differentially expressed (DEGs) CRS analyzed with R software and Venn diagram, biological processes signaling pathways DEGs GO KEGG enrichment. Core screened Betweenness MCC algorithms. GSE164805 GSE171110 dataset used verify expression level core genes. Immunoinfiltration analysis was performed by ssGSEA algorithm GSVA package. DrugBank database analyze for potential therapeutic drugs. Results This study obtained 6950 DEGs, which 971 corresponded (common genes). enrichment showed that multiple associated common closely inflammatory response. Furthermore, revealed transcription factors regulate these are also algorithms gene screening, yielding seven key validation significant differences between normal controls four (feature genes), namely IL6R, TLR4, TLR2, IFNG. upregulated TLR2 mainly Toll-like receptor pathway pathway, while downregulated IFNG primarily participated necroptosis JAK-STAT pathways. Moreover, immune infiltration indicated higher cell mediates In addition, drugs identified via database. Conclusion may be pathogenic targets COVID-19.

Язык: Английский

---