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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 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

Язык: Английский

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Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 7, 2024

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's (PD), and Alzheimer's (AD). Although a great deal energy financial resources have been invested in disease-related research, breakthroughs therapeutic approaches remain elusive. The breakdown cells usually happens together with the onset diseases. However, mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which iron-dependent, causes specific type cell death called ferroptosis, there evidence its involvement pathogenic cascade mechanisms still not well known. present article highlights basic processes underlie ferroptosis corresponding signaling networks. Furthermore, it provides an overview discussion current research on role across variety conditions.

Язык: Английский

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Ferroptosis and myocardial ischemia-reperfusion: mechanistic insights and new therapeutic perspectives

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 1, 2024

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following myocardial infarction. Ferroptosis, type regulated cell death driven by iron and marked lipid peroxidation, has garnered growing interest for its crucial involvement pathogenesis MIRI.This review comprehensively examines mechanisms ferroptosis, focusing on regulation through metabolism, VDAC signaling, antioxidant system dysregulation. We also compare ferroptosis with other forms to highlight distinct characteristics. Furthermore, MIRI examined focus recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit mitigate are reviewed, providing new insights into potential clinical applications.

Язык: Английский

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ROS-mediated ferroptosis and pyroptosis in cardiomyocytes: An update

Life Sciences, Год журнала: 2025, Номер unknown, С. 123565 - 123565

Опубликована: Март 1, 2025

Язык: Английский

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ELANE enhances KEAP1 protein stability and reduces NRF2-mediated ferroptosis inhibition in metabolic dysfunction-associated fatty liver disease

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 9, 2025

Abstract Neutrophil elastase (Elane) is upregulated in metabolic-associated fatty liver disease (MAFLD) and has the capacity to promote progression. However, mechanism by which Elane promotes MAFLD development remains unclear. Ferroptosis, an iron-dependent nonapoptotic form of cell death characterized iron-induced accumulation lipid reactive oxygen species (ROS), been recently considered as important for MAFLD. In this study, we used mice Elane-knockout (Elane-KO) wild-type (WT), their primary mouse hepatocytes establish models vivo vitro elucidating role ferroptosis development. Elane-KO reduced high-fat diet (HFD) induced hepatic peroxidation levels proportion hepatocyte death, expression Nrf2 Gpx4, downregulated Keap1 expression. Treatment with recombinant increased level hepatocytes, rate Keap1, enhanced ubiquitination Nrf2, Gpx4 FFA-induced model. from presented opposite changes. Furthermore, experiment revealed that protein stability thus inhibiting lysosomal degradation protein. Finally, Co-IP experiments weakening binding between P62 ultimately promoted conclusion, our results suggested through P62–Keap1–Nrf2–Gpx4 axis.

Язык: Английский

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Inhibition of Oxidative Stress Contributes to the Protective Effect of Herba Siegesbeckiae on Ischemic Stroke by Pi3k/Stat3/Foxo3a Signal Axis

Опубликована: Янв. 1, 2025

Язык: Английский

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S100A8 induces Cyclophosphamide-Induced Alopecia via NCF2/NOX2-Mediated Ferroptosis

Free Radical Biology and Medicine, Год журнала: 2025, Номер 230, С. 112 - 126

Опубликована: Фев. 11, 2025

Язык: Английский

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Association between methylmalonic acid and prevalence of depression in US adults: evidence from NHANES 2011–2014

European journal of psychotraumatology, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 13, 2025

Background: Depression is a prevalent mental disorder with high morbidity and mortality globally. Methylmalonic acid (MMA) involved in the pathogenesis of numerous diseases. However, it unclear whether there an association between MMA prevalence depression.

Язык: Английский

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Neurotoxicity mechanisms and clinical implications of six common recreational drugs

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 17, 2025

The recreational abuse of addictive drugs poses considerable challenges to public health, leading widespread neurotoxicity and neurological dysfunction. This review comprehensively examines the neurotoxic mechanisms, clinical manifestations, treatment strategies associated with six commonly abused substances: methamphetamine, cocaine, synthetic cathinones, ketamine, nitrous oxide heroin. Despite their diverse pharmacological properties, these converge on shared pathways, including oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation. Psychostimulants, such as cocaine disrupt monoaminergic neurotransmission, causing cognitive impairment, psychiatric disturbances, neurovascular damage. Dissociative anesthetics, ketamine oxide, impair glutamatergic transmission function, thereby exacerbating excitotoxicity neuronal apoptosis. Opioids, heroin, primarily target brain's reward system induce neuroinflammation, cerebrovascular complications. Treatment remain limited, focusing symptomatic management, neuroprotective interventions, behavioral therapies. Emerging approaches, antioxidants, NMDA receptor modulators, rehabilitation, show promise but require further validation. By highlighting underlying mechanisms therapeutic challenges, this provides a foundation for developing targeted interventions advancing research drug-induced neurotoxicity.

Язык: Английский

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Inhibition of oxidative stress contributes to the protective effect of Herba Siegesbeckiae on ischemic stroke by PI3K/STAT3/FOXO3a signal axis

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119688 - 119688

Опубликована: Март 1, 2025

Язык: Английский

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