Ferroptosis inhibitors: past, present and future

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 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.

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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Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 380 - 380

Published: Jan. 4, 2025

Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides comprehensive analysis the effects PSMs on mitochondrial health, with particular emphasis therapeutic potential. Emerging evidence shows that these improve function by reducing oxidative stress, promoting biogenesis, regulating key processes such as apoptosis mitophagy. Mitochondrial dysfunction, hallmark many pathologies, neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, has shown to benefit from protective PSMs. Recent studies show can dynamics, stabilise membranes, enhance bioenergetics, offering significant promise prevention treatment mitochondrial-related diseases. The molecular mechanisms underlying effects, modulation signalling pathways direct interactions proteins, discussed. integration into strategies is highlighted promising avenue improving efficacy while minimising side commonly associated synthetic drugs. also highlights need future research elucidate specific roles individual synergistic within complex plant matrices, may further optimise utility. Overall, this work valuable insights health potential natural agents targeting dysfunction.

Language: Английский

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Effectiveness of Flavonoid-Rich Diet in Alleviating Symptoms of Neurodegenerative Diseases

Foods, Journal Year: 2024, Volume and Issue: 13(12), P. 1931 - 1931

Published: June 19, 2024

Over the past decades, there has been a significant increase in burden of neurological diseases, including neurodegenerative disorders, on global scale. This is linked to widespread demographic trend which developed societies are aging, leading an increased proportion elderly individuals and, concurrently, number those afflicted, posing one main public health challenges for coming decades. The complex pathomechanisms diseases and resulting varied symptoms, differ depending disease, environment, lifestyle patients, make searching therapies this group disorders formidable challenge. Currently, most considered incurable. An important aspect fight against prevention may be broadly understood choices, more specifically, what we will focus review, diet. One proposal that help spread diet rich flavonoids. Flavonoids compounds widely found products healthy, such as fruits, vegetables, herbs. Many studies indicated not only neuroprotective effects these but also their ability reverse changes occurring during progression Alzheimer’s, Parkinson’s amyotrophic lateral sclerosis. Here, present groups flavonoids, discussing characteristics mechanisms action. described point functions due strong antioxidant anti-inflammatory effects, accompanied with penetrate blood-brain barrier, well inhibit formation protein aggregates. latter feature, together promoting removal aggregates especially diseases. We discuss therapeutic potential selected flavonoids based vitro studies, impact when included animals (laboratory research) humans (population studies). Thus, review summarizes flavonoids’ actions impacts Therapeutic use future potentially possible depends overcoming key low bioavailability, determining dose, defining flavonoid-rich its negative effects. suggests further research directions address challenges.

Language: Английский

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Visualizing Intracellular Localization of Natural-Product-Based Chemical Probes Using Click-Correlative Light and Electron Microscopy

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Flavonoids such as sterubin and fisetin─and derivatives thereof─show strong neuroprotective effects in vitro well vivo, combined with negligible toxicity can therefore be considered novel treatment options for neurodegenerative diseases Alzheimer's disease. However, their subcellular locations responsible neuroprotection exact modes of action still remain unclear. Here, we present chemical probes based on both flavonoids fisetin that were utilized fluorescence microscopy click-correlative light electron to detect visualize the localization specific intracellular targets. We successfully adapted workflow correlative a click-chemistry-based approach murine hippocampal cell line (HT22) ultrathin resin sections making visualization small molecule first time possible this setup. Utilizing newly technique, could demonstrate show enrichment endoplasmic reticulum.

Language: Английский

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Nanoparticle-based flavonoid therapeutics: Pioneering biomedical applications in antioxidants, cancer treatment, cardiovascular health, neuroprotection, and cosmeceuticals

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown, P. 125135 - 125135

Published: Dec. 1, 2024

Language: Английский

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Strong Protection by Bazedoxifene Against Chemically-Induced Ferroptotic Neuronal DeathIn Vitro and In Vivo

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

Ferroptosis, a form of regulated cell death associated with iron-dependent lipid peroxidation, can be induced in cultured cells by chemicals (e.g., erastin and RSL3). It has been shown that protein disulfide isomerase (PDI) is mediator chemically-induced ferroptosis also crucial target for protection. The present study reports bazedoxifene (BAZ), selective estrogen receptor modulator, an inhibitor PDI strongly protect against neuronal cells. We find BAZ directly bind to inhibit its catalytic activity. Computational modeling analysis reveals forms hydrogen bond PDI’s His256 residue. Inhibition markedly reduces iNOS nNOS dimerization NO accumulation, these effects are reductions cellular ROS lipid-ROS protection ferroptosis. In addition, the direct antioxidant activity may partially contribute protective effect In vivo animal experiments have mice treated protected kainic acid-induced memory deficits hippocampal damage. Together, results demonstrate potent neurons both in vitro vivo. This work provides evidence receptor-independent, PDI-mediated mechanism neuroprotection BAZ.

Language: Английский

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