Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 280 - 280

Published: Jan. 27, 2023

Neurological and neurodegenerative diseases, particularly those related to aging, are on the rise, but drug therapies rarely curative. Functional disorders organic degeneration of nervous tissue often have complex causes, in which phenomena oxidative stress, inflammation cytotoxicity intertwined. For these reasons, search for natural substances that can slow down or counteract pathologies has increased rapidly over last two decades. In this paper, studies neuroprotective effects flavonoids (especially most widely used, hesperidin quercetin) animal models depression, neurotoxicity, Alzheimer’s disease (AD) Parkinson’s reviewed. The literature topics amounts a few hundred publications vitro vivo (notably rodents) provides us with very detailed picture action mechanisms targets substances. These include decrease enzymes produce reactive oxygen ferroptosis, inhibition mono-amine oxidases, stimulation Nrf2/ARE system, induction brain-derived neurotrophic factor production and, case AD, prevention amyloid-beta aggregation. neuroinflammatory processes been documented as cytokine formation (mainly TNF-alpha IL-1beta) by microglia astrocytes, modulating number regulatory proteins such Nf-kB NLRP3/inflammasome. Although clinical trials humans still scarce, preclinical allow consider hesperidin, quercetin, other interesting safe dietary molecules be further investigated complementary treatments order prevent diseases moderate their deleterious effects.

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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Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and ROS/RNS: Relevance to Parkinson's disease and therapeutic implications

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103092 - 103092

Published: Feb. 16, 2024

In this review, we explore how short-chain fatty acids (SCFAs) produced by the gut microbiome affect Parkinson's disease (PD) through their modulatory interactions with alpha-synuclein, neuroinflammation, and oxidative stress mediated reactive oxygen nitrogen species (ROS/RNS). particular, SCFAs-such as acetate, propionate, butyrate-are involved in gut-brain communication can modulate alpha-synuclein aggregation, a hallmark of PD. The patients PD has lower levels SCFAs than healthy individuals. Probiotics may be potential strategy to restore alleviate symptoms, but underlying mechanisms are not fully understood. Also discuss present guts brains PD, induce neuroinflammation via ROS/RNS. Alpha-synuclein is considered an early biomarker for link axis pathogenesis. Therefore, elucidating role impact on alpha-synuclein-induced microglia ROS/RNS crucial pathogenesis treatment.

Language: Английский

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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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Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 298 - 298

Published: Feb. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Language: Английский

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Ferroptosis: A double-edged sword

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 30, 2024

Abstract Ferroptosis represents a form of programmed cell death that is propelled by iron-dependent lipid peroxidation, thereby being distinguished the prominent features iron accumulation and peroxidation. has been implicated in numerous physiological pathological phenomena, with mounting indications it holds significant implications for cancer other medical conditions. On one side, demonstrates anti-cancer properties triggering ferroptosis within malignant cells, on hand, damages normal cells causing diseases. Therefore, this paper, we propose to review paradoxical regulation tumors First, introduce development history, concept mechanism ferroptosis. The second part focuses methods inducing tumors. third section emphasizes utilization different conditions strategies inhibit fourth elucidates key contradictions control Finally, potential research avenues associated domains are suggested.

Language: Английский

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Brain Iron Metabolism, Redox Balance and Neurological Diseases

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1289 - 1289

Published: June 16, 2023

The incidence of neurological diseases, such as Parkinson’s disease, Alzheimer’s disease and stroke, is increasing. An increasing number studies have correlated these diseases with brain iron overload the resulting oxidative damage. Brain deficiency has also been closely linked to neurodevelopment. These disorders seriously affect physical mental health patients bring heavy economic burdens families society. Therefore, it important maintain homeostasis understand mechanism affecting reactive oxygen species (ROS) balance, in neural damage, cell death and, ultimately, leading development disease. Evidence shown that many therapies targeting ROS imbalances good preventive therapeutic effects on diseases. This review highlights molecular mechanisms, pathogenesis treatment strategies metabolism

Language: Английский

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Engineered Extracellular Vesicle-Based Nanoformulations That Coordinate Neuroinflammation and Immune Homeostasis, Enhancing Parkinson’s Disease Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(34), P. 23014 - 23031

Published: Aug. 15, 2024

Although conventional intervention to microglia can mitigate neuroinflammation in the short term, immune disorders by peripheral inflammatory cells infiltrate continuously, resulting an overactivated microenvironment of Parkinson's disease (PD). Here, we design engineered extracellular vesicle-based nanoformulations (EVNs) address multiple factors for management PD. Specifically, EVN is developed coating CCR2-enriched mesenchymal stem cell-derived vesicles (MSC

Language: Английский

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Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 105 - 132

Published: Jan. 1, 2024

Language: Английский

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α-Synuclein Toxicity in Drosophila melanogaster Is Enhanced by the Presence of Iron: Implications for Parkinson’s Disease

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 261 - 261

Published: Jan. 24, 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by preferential loss of dopaminergic neurons and accumulation intracellular inclusions mainly composed α-synuclein (α-Syn). While etiopathogenesis disorder still elusive, recent experimental evidence supports involvement ferroptosis, an iron-dependent cell death pathway, in pathogenesis PD. In present work, using different ferroptosis inducers inhibitors, we evaluated, vivo, iron α-Syn-mediated toxicity. Using a Drosophila melanogaster model PD based on selective over-expression α-Syn within neurons, demonstrated that promotes protein aggregates, which accompanied neurodegeneration, locomotor impairment, lifespan reduction. These pathological phenotypes were further exacerbated reduced levels glutathione or increased concentrations iron. Coherently, both use chelator presence antioxidant compound N-acetylcysteine exerted protective effects. Overall, our results support

Language: Английский

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