Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Advanced Science, Год журнала: 2023, Номер 10(24)

Опубликована: Июнь 21, 2023

Emerging evidence suggests that ferroptosis, a unique regulated cell death modality is morphologically and mechanistically different from other forms of death, plays vital role in the pathophysiological process neurodegenerative diseases, strokes. Accumulating supports ferroptosis as critical factor diseases strokes, pharmacological inhibition therapeutic target for these diseases. In this review article, core mechanisms are overviewed roles strokes described. Finally, emerging findings treating through This demonstrates by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective treatments highlights potential promising avenue used to prevent article will shed light on developing novel regimens slow down progression future.

Язык: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Язык: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Язык: Английский

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Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 164, С. 114312 - 114312

Опубликована: Май 19, 2023

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its pathogenesis limitations clinical treatment strategies, it poses serious medical challenge burden worldwide. The AD not clear, potential biological mechanisms include aggregation soluble amyloid form insoluble plaques, abnormal phosphorylation tau protein formation intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress metal ion disorders. Among them, ferroptosis newly discovered programmed cell death induced iron-dependent lipid peroxidation reactive oxygen species. Recent studies have shown that closely related AD, but the mechanism remains unclear. may be iron metabolism, amino acid metabolism affecting accumulation ions. Some chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine derivatives, antioxidants (vitamin E, lipoic acid, selenium), derivatives Fer-1, tet, etc. been in animal effective exert neuroprotective effects. This review summarizes regulation natural plant products on order provide reference information for future research development inhibitors.

Язык: Английский

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Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases

Ageing Research Reviews, Год журнала: 2023, Номер 91, С. 102035 - 102035

Опубликована: Авг. 23, 2023

Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), Huntington's (HD), so on. Treating presents opportunities as well challenges for diseases. This review provides a comprehensive overview underlying mechanisms that contribute to occurrence ferroptosis, their implications pathogenesis advancement major disorders. Meanwhile, we summarize interaction between other types diseases contribution corresponding drug development. In addition, specifically recent advances developing therapeutic means targeting these which may guide future approaches effective management devastating medical conditions.

Язык: Английский

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Ferroptosis inhibitors: past, present and future

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Май 23, 2024

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed mechanisms its formation continue to explore effective inhibitors in disease. Recent studies shown correlation between pathological neurodegenerative diseases, as well diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for treatment ferroptosis-mediated diseases. This article specifically describes metabolic pathways summarizes reported action natural synthetic small molecule their efficacy The paper also treatments such gene therapy, nanotechnology, summarises challenges encountered clinical translation inhibitors. Finally, relationship other modes discussed, hopefully paving way future drug design discovery.

Язык: Английский

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Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 2, 2025

Язык: Английский

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Thirty years of NRF2: advances and therapeutic challenges

Nature Reviews Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Язык: Английский

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The Role of Calcium and Iron Homeostasis in Parkinson’s Disease

Brain Sciences, Год журнала: 2024, Номер 14(1), С. 88 - 88

Опубликована: Янв. 17, 2024

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis calcium causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there currently no viable treatment options effective strategies cure delay progression. Pathological hallmarks PD, such as dopaminergic neuronal death intracellular α-synuclein deposition, closely involved perturbations accumulation. Here, we summarize mechanisms by Ca2+ signaling influences promotes progression main ferroptosis Parkinson’s disease. Understanding imbalances contribute this disease critical developing treatments combat devastating disorder.

Язык: Английский

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Natural product-derived ferroptosis mediators

Phytochemistry, Год журнала: 2024, Номер 219, С. 114002 - 114002

Опубликована: Янв. 27, 2024

Язык: Английский

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