From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 18, 2023

Increased production and buildup of reactive oxygen species (ROS) can lead to various health issues, including metabolic problems, cancers, neurological conditions. Our bodies counteract ROS with biological antioxidants such as SOD, CAT, GPx, which help prevent cellular damage. However, if there is an imbalance between these antioxidants, it result in oxidative stress. This cause genetic epigenetic changes at the molecular level. review delves into how plays a role disorders caused by We also look animal models used for researching pathways. study offers insights mechanism, pathology, changes, assist drug development disease understanding.

Language: Английский

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Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 371 - 371

Published: Feb. 25, 2022

Alzheimer’s and Parkinson’s diseases are the two most common forms of neurodegenerative diseases. The exact etiology these disorders is not well known; however, environmental, molecular, genetic influences play a major role in pathogenesis Using disease (AD) as archetype, pathological findings include aggregation Amyloid Beta (Aβ) peptides, mitochondrial dysfunction, synaptic degradation caused by inflammation, elevated reactive oxygen species (ROS), cerebrovascular dysregulation. This review highlights neuroinflammatory neuroprotective epigallocatechin-3-gallate (EGCG): medicinal component green tea, known nutraceutical that has shown promise modulating AD progression due to its antioxidant, anti-inflammatory, anti-aging abilities. report also re-examines current literature provides innovative approaches for EGCG be used preventive measure alleviate other disorders.

Language: Английский

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Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model

Neuropharmacology, Journal Year: 2022, Volume and Issue: 207, P. 108963 - 108963

Published: Jan. 19, 2022

Language: Английский

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New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2698 - 2698

Published: Feb. 26, 2024

Oxidative stress (OS) and inflammation are two important well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence easily oxidizable polyunsaturated fatty acids weak antioxidant defenses, brain is particularly vulnerable oxidative injury. Uncertainty exists over whether these deficits contribute development NDDs or solely a consequence neuronal degeneration. Furthermore, linked, it known that OS can affect inflammatory response. In this review, we will overview last findings about pathways in principal NDDs. Moreover, focus more depth on amyotrophic lateral sclerosis (ALS) understand how anti-inflammatory antioxidants drugs have been used for treatment still incurable motor neuron (MN) disease. Finally, analyze past actual clinical trials future perspectives study mechanisms.

Language: Английский

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The immune system in Parkinson’s disease: what we know so far

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Parkinson's disease (PD) is characterised neuropathologically by the degeneration of dopaminergic neurons in ventral midbrain, accumulation α-synuclein (α-syn) aggregates neurons, and chronic neuroinflammation. In past two decades, vitro, ex vivo studies have consistently shown involvement inflammatory responses mediated microglia astrocytes, which may be elicited pathological α-syn or signals from affected other cell types, are directly linked to neurodegeneration development. Besides prominent immune alterations seen central nervous system (CNS), including infiltration T-cells into brain, more recent demonstrated important changes peripheral profile within both innate adaptive compartments, particularly involving monocytes, CD4+ CD8+ T-cells. This review aims integrate consolidated understanding immune-related processes underlying pathogenesis PD, focusing on cells, neuron-glia crosstalk as well central-peripheral interaction during development PD. Our analysis seeks provide a comprehensive view emerging knowledge mechanisms immunity PD implications this for better overall disease.

Language: Английский

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Free radicals and their impact on health and antioxidant defenses: a review

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 24, 2025

Abstract Free radicals, characterized by the presence of unpaired electrons, are highly reactive species that play a significant role in human health. These molecules can be generated through various endogenous processes, such as mitochondrial respiration and immune cell activation, well exogenous sources, including radiation, pollution, smoking. While free radicals essential for certain physiological signaling defense, their overproduction disrupt delicate balance between oxidants antioxidants, leading to oxidative stress. Oxidative stress results damage critical biomolecules like DNA, proteins, lipids, contributing pathogenesis diseases. Chronic conditions cancer, cardiovascular diseases, neurodegenerative disorders, inflammatory diseases have been strongly associated with harmful effects radicals. This review provides comprehensive overview characteristics types mechanisms formation, biological impacts. Additionally, we explore natural compounds extracts studied antioxidant properties, offering potential therapeutic avenues managing radical-induced damage. Future research directions also discussed advance our understanding treatment radical-associated

Language: Английский

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Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(2), P. 175 - 175

Published: Jan. 28, 2022

Parkinson's disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD considered a multifactorial disease, since both genetic environmental factors contribute its pathogenesis, although molecular mechanisms linking these two key modifiers remain obscure. In this context, epigenetic that alter gene expression without affecting DNA sequence through methylation, histone post-transcriptional modifications, non-coding RNAs may represent mediators of genetic-environmental interactions underlying pathogenesis. Environmental exposures cause chemical alterations in several cellular functions, including expression. Emerging evidence has highlighted smoking, coffee consumption, pesticide exposure, heavy metals (manganese, arsenic, lead, etc.) potentially affect risk development at least partially via modifications. Herein, we discuss recent accumulating pre-clinical clinical impact lifestyle on development, aiming shed more light pathogenesis stimulate future research.

Language: Английский

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Neurodegeneration and Neuroinflammation in Parkinson’s Disease: a Self-Sustained Loop

Current Neurology and Neuroscience Reports, Journal Year: 2022, Volume and Issue: 22(8), P. 427 - 440

Published: June 8, 2022

Abstract Purpose of Review Neuroinflammation plays a significant role in Parkinson’s disease (PD) etiology along with mitochondrial dysfunction and impaired proteostasis. In this context, mechanisms related to immune response can act as modifiers at different steps the neurodegenerative process justify growing interest anti-inflammatory agents potential disease-modifying treatments PD. The discovery inherited gene mutations PD has allowed researchers develop cellular animal models study underlying biology, but original cause neuroinflammation is still debated date. Recent Findings Cell autonomous alterations neuronal cells, including damage protein aggregation, could play role, recent findings also highlighted importance intercellular communication both local systemic level. This given rise debate about non-neuronal cells reignited intense research into gut-brain axis other interactions development disease. Whatever trigger PD, what appears quite clear that aberrant activation glial components system creates vicious circle which neurodegeneration nourish each other. Summary review, we will provide an up-to-date summary main those induced by environmental factors (e.g. gut microbiome) genetic background affected patients. Starting from lesson provided familial forms discuss pathophysiological linked inflammation idiopathic forms. Finally, comment on clinical translatability immunobiomarkers identified patient cohorts update current therapeutic strategies aimed overcoming or preventing

Language: Английский

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Epigallocatechin-3-gallate: A phytochemical as a promising drug candidate for the treatment of Parkinson’s disease

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 12, 2022

Epigallocatechin 3-gallate (EGCG), an abundant polyphenolic component derived from green tea extract, possesses versatile bioactivities that can combat many diseases. During the last decade, EGCG was shown to be effective in experimental models of Parkinson's disease (PD). Several studies have suggested it has pleiotropic neuroprotective effects, which enhanced appeal as a therapeutic strategy PD. In this review, we compiled recent updates and knowledge molecular mechanisms underlying effects We focused on apoptosis, oxidative stress, inflammation, ferroptosis, modulation dopamine production, aggregation α-synuclein. The review highlights pharmacological features its implications Taken together, accumulated data indicate is promising compound for treatment

Language: Английский

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Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2793 - 2793

Published: March 3, 2022

Chronic neuroinflammation has been considered to be involved in the progressive dopaminergic neurodegeneration Parkinson's disease (PD). However, mechanisms remain unknown. Accumulating evidence indicated a key role of blood-brain barrier (BBB) dysfunction neurological disorders. This study is designed elucidate whether chronic damages neurons through BBB by using rotenone-induced mouse PD model. Results showed that rotenone dose-dependently induced nigral neurodegeneration, which was associated with increased Evans blue content and fibrinogen accumulation as well reduced expressions zonula occludens-1 (ZO-1), claudin-5 occludin, three tight junction proteins for maintaining permeability, mice, indicating disruption. Rotenone also microglial activation. Depletion microglia or inhibition activation PLX3397 minocycline, respectively, greatly attenuated rotenone-lesioned mice. Mechanistic inquiry revealed microglia-mediated matrix metalloproteinases-2 9 (MMP-2/-9) contributed disruption neurodegeneration. Rotenone-induced MMP-2/-9 significantly depletion inactivation. Furthermore, wide-range inhibitor, SB-3CT, abrogated elevation permeability simultaneously junctions expression. Finally, we found inactivation ameliorated rotenone-elicited nigrostriatal motor Altogether, our findings suggested activation-mediated model, providing novel view Parkinsonism.

Language: Английский

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