In defence of ferroptosis

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Язык: Английский

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Embryonic development mediated by ferroptotic trigger waves

The Innovation Life, Год журнала: 2025, Номер unknown, С. 100114 - 100114

Опубликована: Янв. 1, 2025

Язык: Английский

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NFE2L2 and ferroptosis resistance in cancer therapy

Cancer Drug Resistance, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

NFE2-like basic leucine zipper transcription factor 2 (NFE2L2, also known as NRF2), is a key in the cellular defense against oxidative stress, playing crucial role cancer cell survival and resistance to therapies. This review outlines current knowledge on link between NFE2L2 ferroptosis - form of regulated death characterized by iron-dependent lipid peroxidation within cells. While activation can protect normal cells from damage, its overexpression contributes drug upregulating antioxidant defenses inhibiting ferroptosis. We delve into molecular pathways ferroptosis, highlighting involvement target genes, such

Язык: Английский

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Inhibition of Mitochondrial Genome-Encoded Mitomir-3 Contributes to Zeb1 Mediated Gpx4 Downregulation and Pro-Ferroptotic Lipid Metabolism to Induce Ferroptosis in Breast Cancer Cells

Опубликована: Янв. 1, 2025

Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, has emerged as unique vulnerability in cancer cells. Existing pro-ferroptotic drugs lack of specificity, low targeting ability, normal tissue toxicity contributing to their limited clinical application therapeutics. Understanding the molecular mechanisms that regulate ferroptosis sensitivity is important for developing precise therapy. The metabolic plasticity cells determines ferroptosis. While altered mitochondrial function contributes reprogramming cells, its role remains be poorly understood. Few studies have identified genome encodes noncoding RNAs. We 13 miRNAs (mitomiRs) are highly expressed breast lines and patient-derived tumor samples. observed higher levels mitomiRs basal-like triple-negative (TNBC) compared mesenchymal stem-like TNBC Interestingly, 11 out bind 3¢UTR zinc finger E-box-binding homeobox 1 (ZEB1) gene. Using mitomiR-3 mimic, inhibitor sponges, we confirmed indeed ZEB1 expression Inhibition induced phenotype basal like Further, showed inhibition contributed upregulation iron metabolism gene expression, decreased proliferation growth along with ferroptotic vivo. Our shows thereby reducing risk off-target effects, making them promising target differential could serve biomarker identify patients who would benefit from inducing study reveals novel link between paving way miRNA-based

Язык: Английский

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Ferroptosis: A Targetable Vulnerability for Melanoma Treatment

Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Melanoma is a devastating form of skin cancer characterized by high mutational burden, limited treatment success, and dismal prognosis. Although immunotherapy targeted therapies have significantly revolutionized melanoma treatment, the majority patients fail to achieve durable responses, highlighting urgent need for novel therapeutic strategies. Ferroptosis, an iron-dependent regulated cell death driven overwhelming accumulation lipid peroxides, has emerged as promising approach in preclinical models. A deeper understanding ferroptosis landscape based on its biology characteristics, including phenotypic plasticity, metabolic state, genomic alterations, epigenetic changes, well complex role mechanisms immune cells could provide foundation developing effective treatments. In this review, we outline molecular ferroptosis, decipher regulation, reveal potential melanoma, discuss pressing questions that should guide future investigations into melanoma.

Язык: Английский

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Multifaceted interplays between the essential players and lipid peroxidation in ferroptosis

Journal of genetics and genomics/Journal of Genetics and Genomics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Ferroptosis: A New Pathway in the Interaction between Gut Microbiota and Multiple Sclerosis

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 6, 2025

Multiple sclerosis (MS) is a chronic autoimmune disorder marked by neuroinflammation, demyelination, and neuronal damage. Recent advancements highlight novel interaction between iron-dependent cell death, known as ferroptosis, gut microbiota, which may significantly influences the pathophysiology of MS. Ferroptosis, driven lipid peroxidation tightly linked to iron metabolism, pivotal contributor oxidative stress observed in Concurrently, affect systemic immunity neurological health, emerges an important regulator homeostasis inflammatory responses, thereby influencing ferroptotic pathways. This review investigates how microbiota dysbiosis ferroptosis impact MS, emphasizing their potential therapeutic targets. Through integrated examination mechanistic pathways clinical evidence, we discuss targeting these interactions could lead interventions that not only modulate disease progression but also offer personalized treatment strategies based on profiling. synthesis aims at deepening insights into microbial contributions implications setting stage for future research exploration.

Язык: Английский

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Metabolic support protects oral mucosa from ferroptosis in radiation-induced mucositis

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Ionizing radiation is effective in combating cancer but inflicts severe damage on the oral mucosa. The mechanisms behind this remain unclear, and current treatment modalities are primarily palliative. This study revealed that ferroptosis predominant reason for oral-radiation depletion of mucosal epithelial cells. More importantly, compensatory activated organism during early stage after exposure. These arise from metabolic support provided by fibroblasts. In post-radiation stage, fibroblasts supply polyamines, which readily absorbed basal cells, protecting them ferroptosis. Local supplementation polyamines effectively mitigates damage. emphasizes important role fibroblast-mediated mucosa radiation-induced Results provide new insights into radiation-related diseases enhancing self-protective responses living organisms.

Язык: Английский

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Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Neonatal anesthesia-related neurological impairments are of significant concern, closely linked to oligodendrocyte dysfunction. However, there is a notable temporal discrepancy between the sustained development oligodendrocytes (myelination) and short-term vulnerability anesthesia exposures. Given rise in iron demand by during neonatal period, our objective was clarify potential roles underlying mechanisms homeostasis, particularly focusing on transferrin receptor 1 (TfR1), governing transient susceptibility anesthesia. Sevoflurane (3 %, 2 h/day) administered wildtype or Pdgfrα-CreERT mice from postnatal day (P)6 P8. Subsequently, behavioral tests, genetic modulation, co-immunoprecipitation assays, Acyl-resin assisted capture assay single-cell RNA sequencing were employed P8 and/or P32. Following exposure sevoflurane, observed cognitive hypomyelination at P32 attributed accumulation ferroptosis, within corpus callosum (CC). This ferroptosis mediated enhanced endocytosis transiently expressed TfR1, rather than its overexpression, due inhibited palmitoylation. Among 21 palmitoyltransferases, only Asp-His-His-Cys5 (DHHC5) down-regulated oligodendrocytes, reducing palmitoylation TfR1 C98 cysteine site. Furthermore, specific overexpression DHHC5 significantly restored endocytosis, hypomyelination, thereby preventing neuronal across multiple brain regions decreasing transport, ultimately mitigating impairments. We discovered that decreased promotes associated resulting initiating impairing cognition following sevoflurane The may mediate critical period for vulnerability. These findings highlight pivotal role TfR1-associated anesthesia-associated neurotoxicity oligodendrocyte-neuron interaction, while providing new perspect understand temporary represent promising therapeutic target enhance safety iron-related disorders.

Язык: Английский

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Interplay between cytokine and FGF2 signaling in induction of entosis and vasculogenic mimicry response in glioblastoma

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

Summary Tumor vascularization is critical to survival of cancer cells, but frequently perturbed leading disorganized angiogenesis and emergence alternative means delivery oxygen nutrients, such as vasculogenic mimicry (VM). Understanding VM its relationship endothelial has been hampered by the lack comprehensive combination in vivo clinical data relevant vitro models. We address this challenge analyzing glioblastoma (GBM) tumors clinically isolated cells. This analysis strongly suggests a key role macrophage-induced controlled cell death VM. The results further point entosis cells intermediate state process, enabled mechano-chemical heterogeneity. find evidence that macrophages can regulate two mechanisms. These reveal mechanistic underpinnings pave way predictive tumor progression.

Язык: Английский

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