Role of iron in brain development, aging, and neurodegenerative diseases

Annals of Medicine, Год журнала: 2025, Номер 57(1)

Опубликована: Март 4, 2025

It is now understood that iron crosses the blood-brain barrier via a complex metabolic regulatory network and participates in diverse critical biological processes within central nervous system, including oxygen transport, energy metabolism, synthesis catabolism of myelin neurotransmitters. During brain development, distributed throughout brain, playing pivotal role key such as neuronal myelination, neurotransmitter synthesis. In physiological aging, can selectively accumulate specific regions, impacting cognitive function leading to intracellular redox imbalance, mitochondrial dysfunction, lipid peroxidation, thereby accelerating aging associated pathologies. Furthermore, accumulation may be primary contributor neurodegenerative diseases Alzheimer's Parkinson's diseases. Comprehending diseases, utilizing iron-sensitive Magnetic Resonance Imaging (MRI) technology for timely detection or prediction abnormal neurological states, implementing appropriate interventions instrumental preserving normal system function.

Язык: Английский

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Dual‐Release Free Iron and Breakdown of Ferroptosis Defenses to Achieve Ferroptosis Cascade Storms for Potent Antitumor Therapy

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 19, 2025

Abstract Ferroptosis is a newly identified type of regulated cell death characterized by iron‐dependent lipid peroxidation. Among the main ferroptosis‐suppressing systems, dihydroorotate dehydrogenase (DHODH)‐ ubiquinone axis closely related to mitochondria and energy metabolism, implying that protects cells from oxidative stress damage via maintenance redox homeostasis. However, ferroptosis initiation requires suitable environment breakthrough in homeostatic limitations systems. Hence, nanoparticles are rationally engineered achieve efficient induction releasing dual‐release free iron disrupting Atovaquone (ATO)‐loaded hollow mesoporous etching zeolitic imidazolate framework‐67 double‐coated oxide/calcium phosphate (Fe 3 O 4 /CaP) conjugated with polyethylene glycol. The external Fe /CaP structure enhances efficiency multiple reactive oxygen species (ROS) generation promoting stress. Still, it achieves increase content unstable pools for igniting ROS storm peroxidation spark. release ATO not only affects metabolism mitochondrial respiratory chain binding complex III but also downregulates DHODH restrict ubiquinol system disrupt Therefore, design this composite nanomedicine provides an approach inducing theoretical basis clinical anti‐tumor trials.

Язык: Английский

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Glial cells improve Parkinson’s disease by modulating neuronal function and regulating neuronal ferroptosis

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 3, 2025

The main characteristics of Parkinson's disease (PD) are the loss dopaminergic (DA) neurons and abnormal aggregation cytosolic proteins. However, exact pathogenesis PD remains unclear, with ferroptosis emerging as one key factors driven by iron accumulation lipid peroxidation. Glial cells, including microglia, astrocytes, oligodendrocytes, serve supportive cells in central nervous system (CNS), but their activation can lead to DA neuron death ferroptosis. This paper explores interactions between glial neurons, reviews changes during pathological process PD, reports on how regulate through homeostasis opens up a new pathway for basic research therapeutic strategies disease.

Язык: Английский

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Natural Compound Emodin Protects Against Mptp Neurotoxicity Via P53-Ferroptosis Inhibition

Опубликована: Янв. 1, 2025

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Язык: Английский

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Loureirin C inhibits ferroptosis and apoptosis in 6-OHDA-induced Parkinson's model

Tissue and Cell, Год журнала: 2025, Номер 93, С. 102721 - 102721

Опубликована: Янв. 8, 2025

Язык: Английский

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Therapeutic Potential of Targeting Ferroptosis in Periprosthetic Osteolysis Induced by Ultra-High-Molecular-Weight Polyethylene Wear Debris

Biomedicines, Год журнала: 2025, Номер 13(1), С. 170 - 170

Опубликована: Янв. 13, 2025

Background/Objectives: Periprosthetic osteolysis is the primary cause of arthroplasty failure in majority patients. Mechanistically, wear debris released from articulating surfaces a prosthesis initiates local inflammation and several modes regulated cell death programs, such as ferroptosis, which represents promising therapeutic target various chronic inflammatory diseases. Thus, current study aimed at exploring potential targeting ferroptosis polyethylene-wear-debris-induced model. Methods: Inverted culture model was used for stimulating cells with vitro, calvarial evaluating effects inhibitors vivo. Results: The immunostaining periprosthetic bone tissues demonstrated number osteocytes expressing markers. Likewise, expressions markers were confirmed polyethylene-wear-debris-stimulated osteocyte-like osteoblasts direct stimulation but not an indirect Furthermore, polyethylene implanted onto mice treated DFO Fer-1. These treatments alleviated pathological resorption induced by implantation. Conclusions: Our data broaden knowledge pathogenesis highlight target.

Язык: Английский

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Euphorbia humifusa Willd. ex Schltdl. Mitigates Liver Injury via KEAP1-NFE2L2-Mediated Ferroptosis Regulation: Network Pharmacology and Experimental Validation

Veterinary Sciences, Год журнала: 2025, Номер 12(4), С. 350 - 350

Опубликована: Апрель 9, 2025

Liver injury poses major health risks in livestock, necessitating effective therapeutic interventions. This study elucidates the hepatoprotective mechanisms of Euphorbia humifusa Willd. ex Schltdl. (EHW) by integrating network pharmacology, molecular docking, and experimental validation. Using a CCl₄-induced liver model mimicking veterinary clinical scenarios, EHW markedly alleviated hepatic damage, demonstrated reduced index, serum ALT AST levels, histopathological lesions, iron accumulation, inflammatory cytokines, ferroptosis-associated gene expression. Network pharmacology identified EHW’s core bioactive components (quercetin, kaempferol, β-sitosterol) critical targets (IL-6, STAT3, HIF-1α, PTGS2, NFE2L2, KEAP1) which were linked to ferroptosis oxidative stress. Molecular docking revealed robust binding affinities between these compounds ferroptosis-related proteins. In vivo validation confirmed that inhibited KEAP1, activated NFE2L2-mediated antioxidant defenses (upregulating SOD1 NQO1), restored homeostasis (lowering TFR1, elevating FTH1), attenuated phospholipid peroxidation suppressing ACSL4 ALOX12. These results indicate mitigates ferroptosis-driven via KEAP1-NFE2L2 signaling restore reduce stress, offering mechanistic foundation for its application hepatoprotection.

Язык: Английский

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Tumoroid Model Reveals Synergistic Impairment of Metabolism by Iron Chelators and Temozolomide in Chemo‐Resistant Patient‐derived Glioblastoma Cells

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 26, 2025

Abstract Chemoresistance poses a significant clinical challenge in managing glioblastoma (GBM), limiting the long‐term success of traditional treatments. Here, 3D tumoroid model is used to investigate metabolic sensitivity temozolomide (TMZ)‐resistant GBM cells iron chelation by deferoxamine (DFO) and deferiprone (DFP). This work shows that TMZ‐resistant acquire stem‐like characteristics, higher intracellular levels, expression aconitase, elevated reliance on oxidative phosphorylation proteins associated with metabolism. Using microphysiological GBM‐on‐a‐chip consisting extracellular matrix (ECM)‐incorporated tumoroids, this demonstrates combination chelators TMZ induces synergistic effect an vitro newly diagnosed recurrent chemo‐resistant patient‐derived reduced their size invasion. Investigating downstream variations reveal iron, increased reactive oxygen species (ROS), upregulated hypoxia‐inducible factor‐1α, viability, autophagy, ribonucleotide reductase (RRM2), arrested proliferation, induced cell death normoxic cells. Hypoxic cells, while showing similar results, display responses deficiency, less blebbing, autophagic flux, suggesting adaptive mechanism hypoxia. These findings show co‐treatment effect, making promising therapy.

Язык: Английский

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The interplay of iron, oxidative stress, and α-synuclein in Parkinson’s disease progression

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Апрель 26, 2025

Abstract The irreversible degeneration of dopamine neurons induced by α-synuclein (α-syn) aggregation in the substantia nigra is central pathological feature Parkinson's disease (PD). Neuroimaging and autopsy studies consistently confirm significant iron accumulation brain PD patients, suggesting a critical role for progression. Current research has established that overload induces ferroptosis dopaminergic neurons, evidence indicates impact on pathology extends beyond ferroptosis. Iron also plays regulatory modulating α-syn, affecting its aggregation, spatial conformation, post-translational modifications, mRNA stability. Iron-induced α-syn can contribute to neurodegeneration through additional mechanisms, potentially creating feedback loop which further enhances accumulation, thus perpetuating vicious cycle neurotoxicity. Given α-syn’s intrinsically disordered structure, targeting metabolism presents promising therapeutic strategy PD. Therefore, development chelators, alone or combination with other drugs, may offer beneficial approach alleviating symptoms slowing

Язык: Английский

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Mechanistic Insights into Cadmium-Induced Nephrotoxicity: NRF2-Driven HO-1 Activation Promotes Ferroptosis via Iron Overload and Oxidative Stress in Vitro

Free Radical Biology and Medicine, Год журнала: 2025, Номер 235, С. 162 - 175

Опубликована: Апрель 29, 2025

Язык: Английский

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