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

Advanced Science, Journal Year: 2023, Volume and Issue: 10(24)

Published: June 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.

Language: Английский

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

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102035 - 102035

Published: Aug. 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.

Language: Английский

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

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114312 - 114312

Published: May 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.

Language: Английский

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Iron/ROS/Itga3 mediated accelerated depletion of hippocampal neural stem cell pool contributes to cognitive impairment after hemorrhagic stroke

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103086 - 103086

Published: Feb. 13, 2024

Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising quality life for affected individuals. Nevertheless, precise underlying mechanism remains elusive. Here, we report first time that accumulation iron within hippocampus, distal to site ICH striatum, is causally linked observed impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) quantitative susceptibility mapping (QSM) demonstrated significant hippocampus patients, which far from actual hematoma. Logistical regression analysis multiple linear identified level as an independent risk factor a negative correlation post-ICH impairment. Using mouse model ICH, triggers excessive activation neural stem cells (NSCs). This overactivation subsequently leads depletion NSC pool, diminished neurogenesis, onset progressive dysfunction. Mechanistically, elevated levels reactive oxygen species (ROS), downregulated expression Itga3. Notably, pharmacological chelation or scavenger aberrant ROS levels, well conditionally overexpressed Itga3 NSCs, remarkably attenuated exhaustion abnormal neurogenesis decline ICH. Together, these results provide molecular insights into ICH-induced shedding light on value maintaining pool preventing dysfunction patients hemorrhagic stroke related conditions.

Language: Английский

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Discovery from Hypericum elatoides and synthesis of hyperelanitriles as α-aminopropionitrile-containing polycyclic polyprenylated acylphloroglucinols

Communications Chemistry, Journal Year: 2024, Volume and Issue: 7(1)

Published: Jan. 2, 2024

Abstract The search for lead compounds with anti-neuroinflammatory activity from structurally ‘optimized’ natural products is a crucial and promising strategy in the quest to discover safe efficacious agents treating neurodegenerative diseases. A phytochemical investigation on aerial portions of Hypericum elatoides led isolation five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A–D ( 1 – 4 ) hyperelamine 5 ). Their structures were determined by spectroscopic analysis, ECD NMR calculations, X-ray crystallography. To best our knowledge, represent first examples featuring an α-aminonitrile moiety, while rare enamine-containing PPAP. Further, synthesis these naturally occurring PPAP-based nitriles or amines was accomplished. Compound exhibited inhibitory against LPS-activated NO production BV-2 cells, potentially through suppression TLR-4/NF-κB signaling. Here we show isolation, structural elucidation, synthesis, bioactive evaluation .

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 2, 2025

Language: Английский

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Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer’s Disease

Antioxidants, Journal Year: 2022, Volume and Issue: 11(4), P. 692 - 692

Published: March 31, 2022

Alzheimer’s disease (AD) is a devastating progressive neurodegenerative characterized by neuronal dysfunction, and decreased memory cognitive function. Iron critical for activity, neurotransmitter biosynthesis, energy homeostasis. accumulation occurs in AD results dysfunction through activation of multifactorial mechanisms. Mitochondria generate iron key co-factor required for: (1) ATP production the electron transport chain, (2) heme protein biosynthesis (3) iron-sulfur cluster formation. Disruptions homeostasis result mitochondrial energetic failure. Ferroptosis, non-apoptotic iron-dependent form cell death mediated uncontrolled reactive oxygen species lipid peroxidation, associated with other diseases. pathogenesis complex multiple diverse interacting players including Aβ-plaque formation, phosphorylated tau, redox stress. Unfortunately, clinical trials based on targeting these canonical hallmarks have been largely unsuccessful. Here, we review evidence linking dysregulation to potential ferroptosis as therapeutic intervention AD.

Language: Английский

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Revisiting the intersection of microglial activation and neuroinflammation in Alzheimer's disease from the perspective of ferroptosis

Chemico-Biological Interactions, Journal Year: 2023, Volume and Issue: 375, P. 110387 - 110387

Published: Feb. 7, 2023

Language: Английский

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Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2812 - 2812

Published: June 13, 2024

Tau protein is a microtubule-associated that widely distributed in the central nervous system and maintains regulates neuronal morphology function. aggregates abnormally forms neurofibrillary tangles neurodegenerative diseases, disrupting structure function of neurons leading to death, which triggers initiation progression neurological disorders. The aggregation tau diseases associated with post-translational modifications, may affect hydrophilicity, spatial conformation, stability protein, promoting formation tangles. Therefore, studying role mechanism aberrant important for understanding finding therapeutic approaches. This review describes possible mechanisms by promotes modifications influencing factors, current status drug discovery development related contribute new approaches alleviate or treat diseases.

Language: Английский

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Natural product-derived ferroptosis mediators

Phytochemistry, Journal Year: 2024, Volume and Issue: 219, P. 114002 - 114002

Published: Jan. 27, 2024

Language: Английский

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