Interaction between macrophages and ferroptosis

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(4)

Published: April 16, 2022

Abstract Ferroptosis, a newly discovered iron-dependent cell death pathway, is characterized by lipid peroxidation and GSH depletion mediated iron metabolism morphologically, biologically genetically different from other programmed deaths. Besides, ferroptosis usually found accompanied inflammatory reactions. So far, it has been participating in the development of many kinds diseases. Macrophages are group immune cells that widely exist our body for host defense play an important role tissue homeostasis mediating inflammation regulating iron, amino acid metabolisms through their unique functions like phagocytosis efferocytosis, cytokines secretion ROS production under polarization. According to these common points characteristics macrophages functions, it’s obvious there must be relationship between ferroptosis. Therefore, review aims at revealing interaction concerning three integrating application certain curing diseases, mostly cancer. Finally, we also provide inspirations further studies therapy some diseases targeting resident distinct tissues regulate Facts Ferroptosis considered as form its nonapoptotic hydroperoxide, metabolisms. playing crucial part various including hepatic neurological cancer, etc. phagocytic cells, existing owning such production. proved participate initiating reactions maintain balance body. Recent try treat cancer altering macrophages’ polarization which damages tumor microenvironment induces cells. Open questions How do specifically? Can use treating than cancer? What can related macrophages? Is more effective therapies when diseases?

Language: Английский

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Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(5), P. 2075 - 2090

Published: Jan. 1, 2022

Ferroptosis and neuroinflammation play crucial roles in Alzheimer's disease (AD) pathophysiology. Forsythoside A (FA), the main constituent of Forsythia suspensa (Thunb.) Vahl., possesses anti-inflammatory, antibacterial, antioxidant, neuroprotective properties. The present study aimed to investigate potential role FA AD neuropathology using male APP/PS1 double transgenic mice, Aβ1-42-exposed N2a cells, erastin-stimulated HT22 LPS-induced BV2 cells. treatment significantly improved mitochondrial function inhibited lipid peroxidation In LPS-stimulated decreased formation pro-inflammatory factors IL-6, IL-1β, NO. ameliorated memory cognitive impairments suppressed Aβ deposition p-tau levels brain. Analyses proteomics, immunohistochemistry, ELISA, western blot revealed that augmented dopaminergic signaling, iron peroxidation, prevented activation IKK/IκB/NF-κB reduced secretion factors, promoted production anti-inflammatory exerted anti-ferroptosis anti-neuroinflammatory effects Nrf2/GPX4 axis played a key these effects. Collectively, results demonstrate protective highlight its therapeutic as drug component for treatment.

Language: Английский

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Cerebral Iron Deposition in Neurodegeneration

Biomolecules, Journal Year: 2022, Volume and Issue: 12(5), P. 714 - 714

Published: May 17, 2022

Disruption of cerebral iron regulation appears to have a role in aging and the pathogenesis various neurodegenerative disorders. Possible unfavorable impacts accumulation include reactive oxygen species generation, induction ferroptosis, acceleration inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow examination macroscopic patterns brain deposits vivo, while modern analytical methods ex vivo enable determination metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes whole brain, cellular, subcellular diseases genetic sporadic origin. We provide an update on mechanisms, biomarkers, effects these disorders, focusing recent publications. In Parkinson’s disease, Friedreich’s several disorders neurodegeneration with group, there is focal siderosis, typically regions most pronounced neuropathological second group including multiple sclerosis, Alzheimer’s amyotrophic lateral sclerosis shows globus pallidus, caudate, putamen, cortical regions. Yet, other such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest diffuse deep gray matter pattern comparable even more extensive than that observed during normal aging. On microscopic level, are mostly dystrophic microglia variably accompanied by iron-laden macrophages astrocytes, implicating changes blood–brain barrier disturbance accumulation. Options potential benefits reducing strategies discussed. Future research investigating whether predispositions play Fe necessary. If confirmed, prevention further uptake individuals at risk may be key for preventing

Language: Английский

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Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 5, 2023

Microglia are the resident innate immune cells in brain with a major role orchestrating responses. They also provide frontline of host defense central nervous system (CNS) through their active phagocytic capability. Being professional phagocyte, microglia participate and autophagic clearance cellular waste debris as well toxic protein aggregates, which relies on optimal lysosomal acidification function. Defective microglial leads to impaired functions result perpetuation neuroinflammation progression neurodegeneration. Reacidification lysosomes has been shown reverse neurodegenerative pathology Alzheimer's disease. In this review, we summarize key factors mechanisms contributing impairment associated dysfunction microglia, how these defects contribute We further discuss techniques monitor pH therapeutic agents that can reacidify under disease conditions. Finally, propose future directions investigate lysosome-mitochondria crosstalk neuron-glia interaction for more comprehensive understanding its broader CNS physiological pathological implications.

Language: Английский

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Iron imbalance in neurodegeneration

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 1139 - 1152

Published: Jan. 12, 2024

Iron is an essential element for the development and functionality of brain, anomalies in its distribution concentration brain tissue have been found to be associated with most frequent neurodegenerative diseases. When magnetic resonance techniques allowed iron quantification vivo, it was confirmed that alteration homeostasis a common feature many However, whether main actor process, or consequence degenerative process still open question. Because different iron-related pathogenic mechanisms are specific distinctive diseases, identifying molecular various pathologies could represent way clarify this complex topic. Indeed, both overload deficiency profound consequences on cellular functioning, contribute neuronal death processes manners, such as promoting oxidative damage, loss membrane integrity, proteostasis, mitochondrial dysfunction. In review, attempt elucidate dyshomeostasis health, we summarize pathological couple death.

Language: Английский

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The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

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The calcium–iron connection in ferroptosis-mediated neuronal death

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 175, P. 28 - 41

Published: Aug. 27, 2021

Language: Английский

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The mechanism of ferroptosis regulating oxidative stress in ischemic stroke and the regulation mechanism of natural pharmacological active components

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 154, P. 113611 - 113611

Published: Sept. 5, 2022

Cerebrovascular diseases, such as ischemic stroke, pose serious medical challenges worldwide due to their high morbidity and mortality limitations in clinical treatment strategies. Studies have shown that reactive oxygen species (ROS)-mediated inflammation, excitotoxicity, programmed cell death of each neurovascular unit during post-stroke hypoxia reperfusion play an important role the pathological cascade. Ferroptosis, a characterized by iron-regulated accumulation lipid peroxidation, is caused abnormal metabolism lipids, glutathione (GSH), iron, can accelerate acute central nervous system injury. Recent studies gradually uncovered process ferroptosis stroke. Some drugs iron chelators, ferrostatin-1 (Fer-1) liproxstatin-1 (Lip-1) protect nerves after injury stroke inhibiting ferroptosis. In addition, combined with our previous on mediated natural compounds this review summarized progress regulation mechanism chemical components herbal recent years, order provide reference information for future research lead development inhibitors.

Language: Английский

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New Target for Prevention and Treatment of Neuroinflammation: Microglia Iron Accumulation and Ferroptosis

ASN NEURO, Journal Year: 2022, Volume and Issue: 14, P. 175909142211332 - 175909142211332

Published: Jan. 1, 2022

Microglia play an important role in maintaining central nervous system homeostasis and are the major immune cells brain. In response to internal or external inflammatory stimuli, microglia activated release numerous factors, thus leading neuroinflammation. Inflammation iron accumulation promote each other jointly progression of Inhibiting prevents Ferroptosis is iron-dependent phospholipid peroxidation-driven type cell death regulation. Cell causes peroxidation membrane phospholipids damages membrane. Ultimately, this process leads ferroptosis. Iron releases a large number factors. Thus, inhibiting ferroptosis may be new target for prevention treatment

Language: Английский

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A proteogenomic view of Parkinson’s disease causality and heterogeneity

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: Feb. 11, 2023

The pathogenesis and clinical heterogeneity of Parkinson's disease (PD) have been evaluated from molecular, pathophysiological, perspectives. High-throughput proteomic analysis cerebrospinal fluid (CSF) opened new opportunities for scrutinizing this heterogeneity. To date, is the most comprehensive CSF-based proteomics profiling study in PD with 569 patients (350 idiopathic patients, 65 GBA + mutation carriers 154 LRRK2 carriers), 534 controls, 4135 proteins analyzed. Combining CSF aptamer-based genetics we determined protein quantitative trait loci (pQTLs). Analyses pQTLs together summary statistics largest genome wide association (GWAS) identified 68 potential causal by Mendelian randomization. top protein, GPNMB, was previously reported to be upregulated substantia nigra patients. We also compared proteomes controls. Proteome differences between unaffected controls suggest degeneration dopaminergic neurons, altered dopamine metabolism increased brain inflammation. In subcohort found dysregulated lysosomal degradation, alpha-synuclein processing, neurotransmission. neuroinflammation, mitochondrial dysfunction/oxidative stress, iron neuroprotection mediated vasoactive substances. Finally, used data stratify into "endotypes". endotypes show cognitive motor progression based on protein-based risk scores.Our findings not only contribute identification therapeutic targets but shape personalized medicine CNS neurodegeneration.

Language: Английский

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