Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Melatonin Alleviates Circadian Rhythm Disruption‐Induced Enhanced Luteinizing Hormone Pulse Frequency and Ovarian Dysfunction

Journal of Pineal Research, Journal Year: 2025, Volume and Issue: 77(1)

Published: Jan. 1, 2025

Circadian rhythm disruption (CRD), stemming from sleep disorders and/or shift work, is a risk factor for reproductive dysfunction. CRD has been reported to disturb nocturnal melatonin signaling, which plays crucial role in female reproduction as circadian regulator and an antioxidant. The hypothalamic-pituitary-ovarian (HPO) axis regulates reproduction, with luteinizing hormone (LH) pulse pattern playing pivotal folliculogenesis steroidogenesis. However, the effect of on HPO involvement remains unclear. Female CBA/CaJ mice underwent modeling, involves alternating between standard light conditions 8-h advance schedule every 3 days 8 weeks, whereas control were maintained under 12:12-h light/dark (LD) cycle. Subsequent measurements diurnal levels, LH patterns assessments via serial tail-tip blood sampling evaluations ovarian function conducted. altered rhythms wheel-running activity secretion led augmented pattern, evidenced by increased frequency, mean pituitary beta-subunit (LHβ) expression, irregular estrous cycles, abnormal luteal function, endocrine oxidative stress. Melatonin treatment (10 mg/kg/day 4 weeks) significantly improved disorder mice, decreasing enhanced frequency LHβ expression. These findings further validated using vitro LβT2 cell perfusion model. Furthermore, restored scavenged reactive oxygen species, thereby preventing apoptosis preserving function. This study offers new insights into impact emphasizes potential supplementation mitigating its effects reproduction.

Language: Английский

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Ferroptosis in Parkinson's disease —— The iron-related degenerative disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102477 - 102477

Published: Aug. 31, 2024

Language: Английский

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Danshen injection ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibiting ferroptosis via activating SIRT1/GPX4 pathway

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 13, 2025

The pathogenesis of renal fibrosis is related to blood stasis, and the method promoting circulation removing stasis often used as treatment principle. Danshen injection (DSI) a commonly drug for in clinic. However, whether DSI slows progression or potential mechanism uncertain. We investigated models using UUO mice TGF-β stimulation HK-2 cells. Our findings revealed that Fer-1 alleviated kidney injury by ameliorating morphology pathological vivo. Besides, inhibited vivo TGF-β-induced Furthermore, ferroptosis was lessened under treatment. More importantly, active ingredients (danshensu, salvianolic acid B, protocatechuic aldehyde, caffeic tanshinone IIA) could bind SIRT1. protein levels SIRT1 GPX4 were downregulated accompanied incremental concentrations Erastin, which repaired intervention. inhibition owing reversed inhibitor EX527. Taken together, our results indicated protect against attenuate activating SIRT1/GPX4 pathway. It expected be agent treat fibrosis.

Language: Английский

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Targeted ErbB4 receptor activation prevents D-galactose-induced neuronal senescence via inhibiting ferroptosis pathway

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

Neuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing significant role. This study aims to investigate the role ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence. Mice subjected D-gal-induced aging were administered small molecule agonist (E4A), identified via virtual screening, melatonin, or combination both. Behavioral assessments conducted evaluate therapeutic efficacy memory and cognitive functions. Immunofluorescence staining, western blot, biochemical assays primarily employed assess changes both senescence- ferroptosis-related molecules mouse hippocampal tissues response each treatment. Additionally, HT22 cell cultures utilized corroborate vivo findings. The targeted by E4A significantly ameliorated behavioral deficits induced D-gal mice, demonstrating an effect comparable that natural inhibitor ferroptosis. Both melatonin mitigated neurons mice. was evidenced upregulation Lamin B1 downregulation P53, P21, P16, GFAP, Iba-1 expression levels. Moreover, treatment markedly decreased protein Nrf2 while augmenting promoter TFRC. These alterations partially reversed individual administration melatonin. In vitro studies further corroborated concurrently markers promoters. However, able reverse these changes. Erastin-induced cells. Our findings suggest may be viable strategy for treating inhibiting ferroptosis, thereby offering potential avenue senescence-associated diseases.

Language: Английский

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Ferroptosis in senescence and age-related diseases: pathogenic mechanisms and potential intervention targets

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 17, 2025

Language: Английский

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Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson’s disease

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 473, P. 134691 - 134691

Published: May 22, 2024

Language: Английский

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The molecular mechanism of ferroptosis and its relationship with Parkinson's disease

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 213, P. 110991 - 110991

Published: May 31, 2024

Neurodegenerative diseases such as Parkinson's disease (PD) have complex pathogenetic mechanisms. Genetic, age, and environmental factors are all related to PD. Due the unclear pathogenesis of PD lack effective cure methods, it is urgent find new targets for treating patients. Ferroptosis a form cell death that reliant on iron exhibits distinct morphological mechanistic characteristics compared other types death. It encompasses range biological processes, including iron/lipid metabolism oxidative stress. In recent years, research has found ferroptosis plays crucial role in pathophysiological processes neurodegenerative stroke. Therefore, also closely PD, This article reviews core mechanisms elucidates correlation between ferroptosis. addition, compounds emerged years exert anti effects by inhibiting signaling pathway were summarized. I hope further elaborate relationship through review this article, provide strategies developing treatments targeting

Language: Английский

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Treating incurable non-communicable diseases by targeting iron metabolism and ferroptosis

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Language: Английский

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Potential role of SIRT1 in cell ferroptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 5, 2025

Ferroptosis is a novel form of cell death that uniquely requires iron and characterized by accumulation, the generation free radicals leading to oxidative stress, formation lipid peroxides, which distinguish it from other forms death. The regulation ferroptosis extremely complex closely associated with spectrum diseases. Sirtuin 1 (SIRT1), NAD + -dependent histone deacetylase, has emerged as pivotal epigenetic regulator potential regulate through wide array genes intricately metabolism, homeostasis, glutathione biosynthesis, redox homeostasis. This review provides comprehensive overview specific mechanisms SIRT1 regulates explores its therapeutic value in context multiple disease pathologies, highlighting significance SIRT1-mediated treatment strategies.

Language: Английский

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