Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 160, P. 92 - 102

Published: Aug. 5, 2020

Language: Английский

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Ferroptosis Mechanisms Involved in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(22), P. 8765 - 8765

Published: Nov. 20, 2020

Ferroptosis is a type of cell death that was described less than decade ago. It caused by the excess free intracellular iron leads to lipid (hydro) peroxidation. Iron essential as redox metal in several physiological functions. The brain one organs known be affected homeostatic balance disruption. Since 1960s, increased concentration central nervous system has been associated with oxidative stress, oxidation proteins and lipids, death. Here, we review main mechanisms involved process ferroptosis such peroxidation, glutathione peroxidase 4 enzyme activity, metabolism. Moreover, association pathophysiology some neurodegenerative diseases, namely Alzheimer’s, Parkinson’s, Huntington’s also addressed.

Language: Английский

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Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 26(1), P. 12 - 26

Published: Dec. 19, 2022

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinson's disease (PD). Iron-loaded microglia are frequently found affected brain regions, but how iron accumulation influences physiology and contributes to neurodegeneration is poorly understood. Here we show that human induced pluripotent stem cell-derived grown a tri-culture system highly responsive susceptible ferroptosis, an iron-dependent form of cell death. Furthermore, overload causes marked shift the microglial transcriptional state overlaps with transcriptomic signature PD postmortem microglia. Our data also this response neurodegeneration, as removal from substantially delayed iron-induced neurotoxicity. To elucidate mechanisms regulating microglia, performed genome-wide CRISPR screen identified novel regulators vesicle trafficking gene SEC24B. These suggest critical role for ferroptosis neurodegeneration.

Language: Английский

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The function and mechanism of ferroptosis in cancer

APOPTOSIS, Journal Year: 2020, Volume and Issue: 25(11-12), P. 786 - 798

Published: Sept. 17, 2020

Language: Английский

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Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review)

Experimental and Therapeutic Medicine, Journal Year: 2022, Volume and Issue: 23(6)

Published: May 6, 2022

Myocardial infarction is one of the primary causes mortality in patients with coronary heart disease worldwide. Early treatment acute myocardial restores blood supply ischemic myocardium and decreases risk. However, when interrupted recovered within a certain period time, it more serious damage to original myocardium; this known as ischemia/reperfusion injury (MIRI). The pathophysiological mechanisms leading MIRI are associated oxidative stress, intracellular calcium overload, energy metabolism disorder, apoptosis, endoplasmic reticulum autophagy, pyroptosis, necroptosis ferroptosis. These interplay another directly or indirectly lead aggravation effect. In past, apoptosis autophagy have attracted attention but ferroptosis also serve key roles. mechanism has not been fully elucidated. present study reviews underlying MIRI. Based on current understanding MIRI, association between cell death‑associated signaling pathways were elaborated, providing direction for investigation novel targets clinical treatment.

Language: Английский

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Dimethyl fumarate improves cognitive deficits in chronic cerebral hypoperfusion rats by alleviating inflammation, oxidative stress, and ferroptosis via NRF2/ARE/NF-κB signal pathway

International Immunopharmacology, Journal Year: 2021, Volume and Issue: 98, P. 107844 - 107844

Published: June 18, 2021

Language: Английский

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Fisetin Attenuates Doxorubicin-Induced Cardiomyopathy In Vivo and In Vitro by Inhibiting Ferroptosis Through SIRT1/Nrf2 Signaling Pathway Activation

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 22, 2022

Doxorubicin (DOX) is an anthracycline antibiotic that used extensively for the management of carcinoma; however, its clinical application limited due to serious cardiotoxic side effects. Ferroptosis represents iron-dependent and reactive oxygen species (ROS)-related cell death has been proven contribute progression DOX-induced cardiomyopathy. Fisetin a natural flavonoid abundantly present in fruits vegetables. It reported exert cardioprotective effects against cardiotoxicity experimental rats. However, underlying mechanisms remain unknown. The study investigated role fisetin molecular mechanism through experiments cardiomyopathy rat H9c2 models. results revealed treatment could markedly abate by alleviating cardiac dysfunction, ameliorating myocardial fibrosis, mitigating hypertrophy rats, attenuating ferroptosis cardiomyocytes reversing decline GPX4 level. Mechanistically, exerted antioxidant effect reducing MDA lipid ROS levels increasing glutathione (GSH) Moreover, protective SIRT1 expression Nrf2 mRNA protein nuclear translocation, which resulted activation downstream genes such as HO-1 FTH1. Selective inhibition attenuated cells, turn decreased GSH levels, well Nrf2, HO-1, FTH1 expressions. In conclusion, exerts therapeutic inhibiting via SIRT1/Nrf2 signaling pathway activation.

Language: Английский

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Ferroptosis as a mechanism of neurodegeneration in Alzheimer's disease

Journal of Neurochemistry, Journal Year: 2021, Volume and Issue: 159(5), P. 804 - 825

Published: Sept. 23, 2021

Alzheimer's disease (AD) is the most prevalent form of dementia, with complex pathophysiology that not fully understood. While β-amyloid plaque and neurofibrillary tangles define pathology disease, mechanism neurodegeneration uncertain. Ferroptosis an iron-mediated programmed cell death characterised by phospholipid peroxidation has been observed in clinical AD samples. This review will outline growing molecular evidence implicating ferroptosis pathogenesis AD, implications for disease-modifying therapies.

Language: Английский

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Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Ferroptosis is a nonapoptotic form of cell death characterized by iron‐dependent accumulation lipid hydroperoxides to lethal levels. Necroptosis, an alternative programmed necrosis, regulated receptor‐interacting protein (RIP) 1 activation and RIP3 mixed‐lineage kinase domain‐like (MLKL) phosphorylation. necroptosis both play important roles in the pathological progress ischemic stroke, which complex brain disease several pathways. In past few years, increasing evidence has suggested that crosstalk occurs between ferroptosis stroke. However, potential links stroke have not been elucidated yet. Hence, this review, we overview analyze mechanism underlying And find iron overload, one ferroptosis, leads mitochondrial permeability transition pore (MPTP) opening, aggravates RIP1 phosphorylation contributes necroptosis. addition, heat shock 90 (HSP90) induces promoting suppressing glutathione peroxidase 4 (GPX4) activation. work, try deliver new perspective exploration novel therapeutic targets for treatment

Language: Английский

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Iron Homeostasis Disorder and Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12442 - 12442

Published: Nov. 18, 2021

Iron is an essential trace metal for almost all organisms, including human; however, oxidative stress can easily be caused when iron in excess, producing toxicity to the human body due its capability both electron donor and acceptor. Although there a strict regulation mechanism homeostasis brain, it usually inevitably disturbed by genetic environmental factors, or disordered with aging, which leads metabolism diseases, many neurodegenerative diseases such as Alzheimer’s disease (AD). AD one of most common degenerative central nervous system (CNS) threatening health. However, precise pathogenesis still unclear, seriously restricts design interventions treatment drugs based on AD. Many studies have observed abnormal accumulation different regions resulting cognitive, memory, motor other nerve damages. Understanding metabolic balance brain crucial AD, would provide new cures disease. This paper reviews recent progress relationship between from aspects absorption intestinal cells, storage cells organs, especially prospects future directions treatments.

Language: Английский

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