Ironing out the role of ferroptosis in immunity

Immunity, Journal Year: 2024, Volume and Issue: 57(5), P. 941 - 956

Published: May 1, 2024

Ferroptosis is a type of regulated cell death that drives the pathophysiology many diseases. Oxidative stress detectable in types death, but only ferroptosis involves lipid peroxidation and iron dependency. originates propagates from several organelles, including mitochondria, endoplasmic reticulum, Golgi, lysosomes. Recent data have revealed immune cells can both induce undergo ferroptosis. A mechanistic understanding how regulates immunity critical to controls responses this dysregulated disease. Translationally, more work needed produce ferroptosis-modulating immunotherapeutics. This review focuses on role immune-related diseases, infection, autoimmune cancer. We discuss immunity, regulation contributes disease pathogenesis, targeting may lead novel therapies.

Language: Английский

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Ferroptosis: a new hunter of hepatocellular carcinoma

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 13, 2024

Abstract Ferroptosis is an iron ion-dependent, regulatory cell death modality driven by intracellular lipid peroxidation that plays a key role in the development of HCC. Studies have shown various clinical agents (e.g., sorafenib) ferroptosis inducer-like effects and can exert therapeutic modulating different factors pathway. This implies targeting tumor may be very promising strategy for therapy. In this paper, we summarize prerequisites defense systems occurrence targets drug-mediated action HCC, differences connections between other programmed deaths. We aim to theoretical basis, classical inducers research progress HCC cells, clued treatment regulating network. Further investigation specific mechanisms hepatocellular carcinoma interventions at stages will help us deepen our understanding carcinoma, with view providing new more precise preventive as well measures patients.

Language: Английский

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Ferroptosis inhibitors: past, present and future

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 23, 2024

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed mechanisms its formation continue to explore effective inhibitors in disease. Recent studies shown correlation between pathological neurodegenerative diseases, as well diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for treatment ferroptosis-mediated diseases. This article specifically describes metabolic pathways summarizes reported action natural synthetic small molecule their efficacy The paper also treatments such gene therapy, nanotechnology, summarises challenges encountered clinical translation inhibitors. Finally, relationship other modes discussed, hopefully paving way future drug design discovery.

Language: Английский

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In defence of ferroptosis

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 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

Language: Английский

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A novel silkworm excrement-derived nanomedicine integrating ferroptosis and photodynamic therapy, well-suitable for PD-L1-mediated immune checkpoint blockade

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 505, P. 159676 - 159676

Published: Jan. 17, 2025

Language: Английский

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Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 334 - 334

Published: Feb. 26, 2025

In recent years, ferroptosis, as an emerging modality of programmed cell death, has captured significant attention within the scientific community. This comprehensive review meticulously canvasses pertinent literature past few spanning multiple facets. It delves into intricate mechanisms underpinning tracks evolution its inducers and inhibitors, dissects roles in a diverse array diseases, well resultant therapeutic implications. A profound exploration is conducted functional ferroptosis-related molecules, intracellular pathways, metabolic cascades, signaling transduction routes. Novel ferroptosis inhibitors are introduced detail, covering their design blueprints, synthetic methodologies, bioactivity profiles. Moreover, exhaustive account provided regarding involvement malignancies, neurodegenerative disorders, cardiovascular ailments, other pathologies. By highlighting pivotal status potential regimens various this aspires to furnish thorough reference framework for future investigations clinical translations domain.

Language: Английский

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Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7544 - 7544

Published: July 9, 2024

Ferroptosis is a type of nonapoptotic cell death that characteristically caused by phospholipid peroxidation promoted radical reactions involving iron. Researchers have identified many the protein factors are encoded genes promote ferroptosis. Glutathione peroxidase 4 (GPX4) key enzyme protects phospholipids from and suppresses ferroptosis in glutathione-dependent manner. Thus, dysregulation involved cysteine and/or glutathione metabolism closely associated with From perspective dynamics, actively proliferating cells more prone to than quiescent cells, which suggests species generated during oxygen-involved responsible for lipid peroxidation. Herein, we discuss initial events dominantly occur process energy metabolism, association deficiency. Accordingly, tricarboxylic acid cycle coupled respiratory chain mitochondria main subjects here, this likely source both electrons free Since not only carbohydrates, but also amino acids, especially glutamate, major substrates central dealing nitrogen derived groups contributes subject discussion.

Language: Английский

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Ferroptosis: Biology and Role in Gastrointestinal Disease

Gastroenterology, Journal Year: 2024, Volume and Issue: 167(2), P. 231 - 249

Published: March 1, 2024

Language: Английский

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Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies

Cancers, Journal Year: 2024, Volume and Issue: 16(6), P. 1220 - 1220

Published: March 20, 2024

Based on the multifaceted molecular machinery that tightly controls iron cellular homeostasis, this review delves into its paradoxical, potentially dangerous role in biological systems, with a special focus double-edged sword correlations cancer. Indeed, though is vital micronutrient and required cofactor participating several essential cell functions, tendency to cause oxidative stress can be related both cancer risk activation of death pathways. In scenario, ferroptosis refers an iron-dependent form regulated (RCD) powered by overload lethal peroxides sharing distinctive oxidized phospholipid profiles. As unique pathway, morphologically mechanistically different from other types programmed involving executioner family proteins. The accumulation cytotoxic lipid encompasses antagonism between execution defense occurring when ferroptosis-promoting activities significantly exceed antioxidant defenses. most recent breakthroughs have aroused great consideration tumor biology, as targeting provide new tools for exploring therapeutic strategies suppression. Mutations death/survival pathway alterations, well metabolic regulations cells, including propensity generate ROS, are seen features render cells unprotected ferroptosis, thereby exposing vulnerabilities which deserve further attention regarded targetable cancers limited options.

Language: Английский

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Cr(VI) induces ferroptosis in DF-1 cells by simultaneously perturbing iron homeostasis of ferritinophagy and mitophagy

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 925, P. 171818 - 171818

Published: March 19, 2024

Language: Английский

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