Ferroptosis in health and disease

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 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

Language: Английский

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Oxidative Stress and Neuroinflammation in Parkinson’s Disease: The Role of Dopamine Oxidation Products

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 955 - 955

Published: April 18, 2023

Parkinson’s disease (PD) is a chronic neurodegenerative condition affecting more than 1% of people over 65 years old. It characterized by the preferential degeneration nigrostriatal dopaminergic neurons, which responsible for motor symptoms PD patients. The pathogenesis this multifactorial disorder still elusive, hampering discovery therapeutic strategies able to suppress disease’s progression. While redox alterations, mitochondrial dysfunctions, and neuroinflammation are clearly involved in pathology, how these processes lead neurons an unanswered question. In context, presence dopamine itself within neuronal population could represent crucial determinant. present review, attempt made link aforementioned pathways oxidation chemistry dopamine, leading formation free radical species, reactive quinones toxic metabolites, sustaining pathological vicious cycle.

Language: Английский

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Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(5), P. 2166 - 2184

Published: Jan. 26, 2024

Environmental pollutants have been recognized for their ability to induce various adverse outcomes in both the environment and human health, including inflammation, apoptosis, necrosis, pyroptosis, autophagy. Understanding these biological mechanisms has played a crucial role risk assessment management efforts. However, recent identification of ferroptosis as form programmed cell death emerged critical mechanism underlying pollutant-induced toxicity. Numerous studies demonstrated that fine particulates, heavy metals, organic substances can trigger ferroptosis, which is closely intertwined with lipid, iron, amino acid metabolism. Given growing evidence linking severe diseases such heart failure, chronic obstructive pulmonary disease, liver injury, Parkinson's Alzheimer's cancer, it imperative investigate ferroptosis. In this review, we comprehensively analyze pathways intricate signaling molecules elucidate integration into driving braking axes. Furthermore, discuss potential hazards associated organs four representative animal models. Finally, provide an outlook on future research directions strategies aimed at preventing By enhancing our understanding novel developing effective preventive measures, mitigate effects environmental safeguard health.

Language: Английский

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Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho‐1/Gpx4 pathway to prevent α‐synuclein‐induced ferroptosis in Parkinson's disease

Journal of Pineal Research, Journal Year: 2024, Volume and Issue: 76(2)

Published: March 1, 2024

Abstract Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation α‐synuclein (α‐syn). Ferroptosis, form cell death induced iron accumulation lipid peroxidation, involved in pathogenesis PD. It unknown whether melatonin receptor 1 (MT1) modulates α‐syn ferroptosis Here, we used preformed fibrils (PFFs) to induce PD models vivo vitro. In mice, led increased deposition ferroptosis. MT1 knockout exacerbated these changes resulted more DA neuronal severe motor impairment. also suppressed Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance ferroptosis, inhibited expression ferritin Fth1, leading release ferrous ions. vitro experiments confirmed findings. Knockdown enhanced PFF‐induced intracellular pathway Fth1 protein, thereby aggravating Conversely, overexpression reversed effects. Our findings reveal novel mechanism which activation prevents α‐syn‐induced PD, highlighting neuroprotective role

Language: Английский

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The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4269 - 4269

Published: April 12, 2024

Iron accumulation in the brain is a common feature of many neurodegenerative diseases. Its involvement spans across main proteinopathies involving tau, amyloid-beta, alpha-synuclein, and TDP-43. Accumulating evidence supports contribution iron disease pathologies, but delineation its pathogenic role yet challenged by complex multiple neurotoxicity mechanisms supporting reciprocal influence between protein pathology. Here, we review major proteinopathy-specific observations four distinct hypotheses: (1) deposition consequence pathology; (2) promotes (3) protects from or hinders (4) pathology contribute parallelly to pathogenesis. an essential element for physiological function, requiring fine balance levels. Understanding disease-related at more intricate systemic level critical advancements chelation therapies.

Language: Английский

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The molecular mechanism of ferroptosis and its relationship with Parkinson's disease

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 213, P. 110991 - 110991

Published: May 31, 2024

Neurodegenerative diseases such as Parkinson's disease (PD) have complex pathogenetic mechanisms. Genetic, age, and environmental factors are all related to PD. Due the unclear pathogenesis of PD lack effective cure methods, it is urgent find new targets for treating patients. Ferroptosis a form cell death that reliant on iron exhibits distinct morphological mechanistic characteristics compared other types death. It encompasses range biological processes, including iron/lipid metabolism oxidative stress. In recent years, research has found ferroptosis plays crucial role in pathophysiological processes neurodegenerative stroke. Therefore, also closely PD, This article reviews core mechanisms elucidates correlation between ferroptosis. addition, compounds emerged years exert anti effects by inhibiting signaling pathway were summarized. I hope further elaborate relationship through review this article, provide strategies developing treatments targeting

Language: Английский

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Alpha-synuclein interaction with mitochondria is the final mechanism of ferroptotic death induced by erastin in SH-SY5Y cells

Free Radical Research, Journal Year: 2024, Volume and Issue: 58(3), P. 217 - 228

Published: March 3, 2024

Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation reactive oxygen species and lipid oxidation products along with typical morphological alterations in mitochondria. is activated diverse triggers inhibited ferrostatin-1 liproxstatin-1, apart from iron chelators several antioxidants, the process implicated multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially regarding final executioner subsequent to ROS. This study uses inducer ferroptosis such erastin on SH-SY5Y cells, shows clearly that ferroptotic cells loss mitochondrial membrane potential intracellular ATP content oxidative stress markers. All these are prevented liproxstatin-1. Additionally, cyclosporine A prevents induced implying crucial role permeability transition pore (mPTP) activation death. Furthermore, α-synuclein occurs during which can be When knock-down expression performed specific siRNA treatment impairment markedly prevented. Thus, through involvement mPTP appears key protein erastin, but it needs verified if generalized mechanism using other inducers lines.

Language: Английский

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Biomarkers of Parkinson’s Disease: From Basic Research to Clinical Practice

Aging and Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Parkinson’s disease (PD) is a common neurodegenerative characterized pathologically by dopaminergic neuron loss and the formation of Lewy bodies, which are enriched with aggregated α-synuclein (α-syn). PD currently has no cure, but therapeutic strategies available to alleviate symptoms. Early diagnosis can greatly improve interventions, clinical remains challenging depends mainly on features imaging tests. Efficient specific biomarkers crucial for diagnosis, monitoring, evaluation PD. Here, we reviewed in different tissues biofluids, along current biochemical detection methods. We found that sensitivity specificity single limited, selecting appropriate indicators combined diagnostic accuracy

Language: Английский

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Synucleinopathies Take Their Toll: Are TLRs a Way to Go?

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1231 - 1231

Published: April 24, 2023

The misfolding and subsequent abnormal accumulation aggregation of α-Synuclein (αSyn) as insoluble fibrils in Lewy bodies neurites is the pathological hallmark Parkinson's disease (PD) several neurodegenerative disorders. A combination environmental genetic factors linked to αSyn misfolding, among which neuroinflammation recognized play an important role. Indeed, a number studies indicate that Toll-like receptor (TLR)-mediated might lead dopaminergic neural loss, suggesting TLRs could participate pathogenesis PD promoters immune/neuroinflammatory responses. Here we will summarize our current understanding on mechanisms focusing contribution progression α-synucleinopathies speculating their link with non-motor disturbances associated aging

Language: Английский

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