Iron overload‐induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: An in vitro and in vivo study

IUBMB Life, Год журнала: 2022, Номер 74(11), С. 1052 - 1069

Опубликована: Май 31, 2022

Abstract Growing evidence indicates that iron overload is an independent risk factor for osteoporosis. However, the mechanisms are not fully understood. The purpose of our study was to determine whether could lead ferroptosis in osteoblasts and explore involved overload‐induced osteoporosis vitro vivo. Ferric ammonium citrate used mimic conditions, while deferoxamine ferrostatin‐1 were inhibit MC3T3‐E1 cells vitro. ferroptosis, osteogenic differentiation mineralization assessed A mouse model established using dextran. Immunohistochemical analysis performed Enzyme‐linked immunosorbent assays calcein–alizarin red S labelling assess new bone formation. Dual x‐ray absorptiometry, micro‐computed tomography histopathological conducted evaluate results showed reduced cell viability, superoxide dismutase glutathione levels, increased reactive oxygen species generation, lipid peroxidation, malondialdehyde levels ferroptosis‐related protein expression, induced ultrastructural changes mitochondria. Iron also Inhibiting reversed described above. inhibited osteogenesis, promoted vivo, which be improved by ferrostatin‐1. These demonstrate plays a crucial role Maintaining homeostasis targeting might potential measures treating or preventing

Язык: Английский

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Therapeutic inhibition of ferroptosis in neurodegenerative disease

Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(10), С. 674 - 688

Опубликована: Авг. 30, 2023

Язык: Английский

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Iron homeostasis in older adults: balancing nutritional requirements and health risks

The journal of nutrition health & aging, Год журнала: 2024, Номер 28(5), С. 100212 - 100212

Опубликована: Март 14, 2024

Iron plays a crucial role in many physiological processes, including oxygen transport, bioenergetics, and immune function. is assimilated from food also recycled senescent red blood cells. exists two dietary forms: heme (animal based) non-heme (mostly plant based). The body uses iron for metabolic purposes, stores the excess mainly splenic hepatic macrophages. Physiologically, excretion humans inefficient not highly regulated, so regulation of intestinal absorption maintains homeostasis. losses occur at steady rate via turnover epithelium, loss, exfoliation dead skin cells, but overall homeostasis tightly controlled cellular systemic levels. Aging can have profound impact on induce dyshomeostasis where deficiency or overload (sometimes both simultaneously) occur, potentially leading to several disorders pathologies. To maintain physiologically balanced levels, reduce risk disease, promote healthy aging, it advisable older adults follow recommended daily intake guidelines periodically assess Clinicians evaluate status using different techniques selecting an assessment method primarily depends condition being examined. This review provides comprehensive overview forms, sources, metabolism iron, associated dyshomeostasis, levels adults, nutritional strategies balance adults.

Язык: Английский

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The Role of Microglia in Alzheimer’s Disease From the Perspective of Immune Inflammation and Iron Metabolism

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Июнь 30, 2022

Alzheimer’s disease (AD), the most common type of senile dementia, includes complex pathogenesis abnormal deposition amyloid beta-protein (Aβ), phosphorylated tau (p-tau) and neuroimmune inflammatory. The neurodegenerative process AD triggers microglial activation, overactivation microglia produces a large number inflammatory factors. Microglia dysfunction can lead to disturbances in iron metabolism enhance iron-induced neuronal degeneration AD, while elevated levels brain areas affect phenotype function. In this manuscript, we firstly discuss role then introduce immune-inflammatory pathology AD. Their homeostasis is emphasized. Recent studies on ferroptosis are also reviewed. It will help readers better understand provides basis for regulation disorders discovery new potential therapeutic targets

Язык: Английский

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Ferroptosis: mechanisms and therapeutic targets

MedComm, Год журнала: 2024, Номер 5(12)

Опубликована: Ноя. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

Язык: Английский

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Targeting ferroptosis: a new therapeutic opportunity for kidney diseases

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 3, 2024

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and characterized by the accumulation lipid peroxides to lethal levels. involves multiple pathways including redox balance, regulation, mitochondrial function, amino acid, lipid, glycometabolism. Furthermore, various disease-related signaling also play role in regulating process oxidation. In recent years, with emergence concept ferroptosis in-depth study its mechanisms, closely associated biological conditions related kidney diseases, organ development, aging, immunity, cancer. This article reviews development ferroptosis, mechanisms (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, MBOAT1/2 pathways), latest research progress involvement diseases. It summarizes diseases within frameworks metabolism, reactive oxygen biology, biology. The introduces key regulatory factors as well important concepts major open questions natural compounds. hoped future research, further breakthroughs can be made understanding regulation mechanism utilizing promote treatments for such acute injury(AKI), chronic disease (CKD), diabetic nephropathy(DN), renal carcinoma. paves way new approach prevent, treat clinical

Язык: Английский

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Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1462 - 1462

Опубликована: Ноя. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Язык: Английский

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

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 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.

Язык: Английский

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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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17β-oestradiol inhibits ferroptosis in the hippocampus by upregulating DHODH and further improves memory decline after ovariectomy

Redox Biology, Год журнала: 2023, Номер 62, С. 102708 - 102708

Опубликована: Апрель 23, 2023

Ovariectomy (OVX) conducted before the onset of natural menopause is considered to bringing forward and accelerate process ageing-associated neurodegeneration. However, mechanisms underlying memory decline other cognitive dysfunctions following OVX are unclear. Given that iron accumulates during ageing after OVX, we hypothesized excess accumulation in hippocampus would cause ferroptosis-induced increased neuronal degeneration death associated with decline. In current study, female rats underwent showed decreased dihydroorotate dehydrogenase (DHODH) expression reduced performance Morris water maze (MWM). We used primary cultured hippocampal cells explore ferroptosis resistance–inducing effect 17β-oestradiol (E2). The data supported a vital role DHODH ferroptosis. Specifically, E2 alleviated induced by erastin ferric ammonium citrate (FAC), which can be blocked brequinar (BQR). Further vitro studies lipid peroxidation levels improved behavioural rats. Our research interprets OVX-related neurodegeneration respect ferroptosis, both our vivo show supplementation exerts beneficial antiferroptotic effects upregulating DHODH. demonstrate utility provide potential target, DHODH, for hormone therapy has not been available.

Язык: Английский

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