Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 149 - 149

Published: Jan. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Language: Английский

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Adverse Outcome Pathway-Based Strategies to Mitigate Ag₂Se Quantum Dot-Induced Neurotoxicity

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Silver selenide quantum dots (Ag2Se QDs) show great advantages in tumor imaging due to their excellent optical performance and good biocompatibility. However, the ultrasmall particle size of Ag2Se QDs allows them cross blood-brain barrier, thus potentially affecting central nervous system. Therefore, risk assessment response strategies for are important. The adverse outcome pathway (AOP) framework makes it possible develop management based on toxicity mechanisms. In this study, using AOP framework, we constructed causal mechanism relationship diagrams at different biological levels QD neurotoxicity. excess mitochondrial reactive oxygen species (mtROS) triggered Nod-like receptor protein 3 (NLRP3) inflammasome activation microglia was molecular initiation event (MIE). Proinflammatory mediator secretion were key events (KEs) cellular level. Neuroinflammation neuronal damage KEs organ/tissue Altered hippocampal physiology (AO) individual Based established further studies confirmed that mtROS-activated nuclear-factor-E2-related factor 2 (Nrf2)/PTEN-induced kinase 1 (PINK1)- mitophagy contributed weaken MIE. Molecular docking-assisted biology experiments demonstrated quercetin (Qu) enhanced process. This article emphasizes importance nanomaterials. Furthermore, paper guides use natural small-molecule drugs as a strategy mitigate nanomaterial-induced

Language: Английский

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Therapeutic potential of Baicalin against experimental obsessive compulsive disorder: Evidence from CSF, blood plasma, and brain analysis

Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: unknown, P. 578598 - 578598

Published: March 1, 2025

Language: Английский

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Disrupted mitochondrial transcription factor A expression promotes mitochondrial dysfunction and enhances ocular surface inflammation by activating the absent in melanoma 2 inflammasome

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 222, P. 106 - 121

Published: May 24, 2024

Severe dry eye disease causes ocular surface damage, which is highly associated with mitochondrial dysfunction. Mitochondrial transcription factor A (TFAM) essential for packaging DNA (mtDNA) and crucial maintaining function. Herein, we aimed to explore the effect of a decreased TFAM expression on damage.

Language: Английский

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Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 302 - 302

Published: Feb. 28, 2025

Excessive alcohol consumption significantly impacts human health, particularly the brain, due to its susceptibility oxidative stress, which contributes neurodegenerative conditions. Alcohol metabolism in brain occurs primarily via catalase, followed by CYP2E1 pathways. Excess metabolized generates reactive oxygen/nitrogen species (ROS/RNS), leading cell injury altering many different Elevated stress impairs autophagic processes, increasing post-translational modifications and further exacerbating mitochondrial dysfunction ER death. The literature highlights that alcohol-induced disrupts autophagy mitophagy, contributing neuronal damage. Key mechanisms include dysfunction, epigenetics, accumulation of oxidatively modified proteins, lead neuroinflammation impaired cellular quality control. These processes are exacerbated chronic exposure, resulting suppression protective pathways like NRF2-mediated antioxidant responses increased changes brain. Alcohol-mediated neurotoxicity involves complex interactions between metabolism, regulation, influenced various factors such as drinking patterns, nutritional status, genetic/environmental factors, highlighting need for molecular studies unravel these develop targeted interventions.

Language: Английский

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BNIP3-mediated mitophagy aggravates placental injury in preeclampsia via NLRP1 inflammasome

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 2, 2025

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by pronounced placental oxidative stress and inflammatory damage. However, the contribution mitophagy to inflammation-induced injury in PE remains unclear. Human placenta samples were collected from 15 normal pregnant women preeclampsia women. Protein expression was analyzed western blotting, while immunofluorescence staining employed localize mediators. Mitochondrial reactive oxygen species quantified using MitoSOX. The concentrations pro-inflammatory cytokines ELISA, ultrastructural alterations evaluated transmission electron microscopy. To investigate molecular mechanisms vivo, mouse model established via daily subcutaneous administration L-NAME, followed tail vein delivery AAV9 carrying shRNA for targeted gene knockdown. In this study, we demonstrate that BNIP3-mediated NLRP1 inflammasome activation occur an L-NAME-induced human placenta. results also indicate knockdown BNIP3 abolishes JEG3 cells H/R condition, suggesting positive regulatory role controlling NLRP1-dependent inflammation. Furthermore, silencing leads significant reduction mitochondrial damage mtROS production. Treatment with MitoTEMPO after further decreases NLRP1, overexpression nullifies impact Additionally, alleviates model. These findings reveal novel mechanism through which exacerbates H/R-induced inducing production activating PE.

Language: Английский

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Effects of Dictyophora polysaccharide on cerebellar Purkinje cell degeneration in a chronic alcohol mouse model

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

Abstract Background Recent research showed that the NLRP3 inflammasome was activated in central nervous system of mice administered chronic ethanol (EtOH). Dictyophora polysaccharides (DIPs) are essential components valuable edible fungus , which has antioxidant properties can delay aging process body. This study aimed to investigate roles EtOH‐induced cerebellar Purkinje cell (PC) degeneration and behavioral changes. Methods C57BL/6J normal knockout were exposed EtOH for 14 days. polysaccharide (DIP) inhibitor mice. The pathology NLRP3‐ASC‐caspase‐1 signaling pathway proteins analyzed tissues performance assessed Results In mouse model, we observed increases proteins, including NLRP3, ASC, caspase‐1, mature IL‐1β pro IL‐1β, loss PCs, motor coordination disorders. We found DIPs could suppress pathway, alleviate deficits pathological changes Next, used MCC950, a inhibitor, an strategy further verify effects MCC950 or alleviated latency decreases fall time, stride width length. also attenuated PC number suppressed inflammation induced by EtOH. Taken together, pharmacologically genetically inhibiting deficits. Conclusion These findings indicated might diminish through provides potential therapeutic target prevention treatment alcoholism pathology.

Language: Английский

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Ginsenoside Re Inhibits NLRP3 Inflammasome Activation in Depressive Mice by Promoting PINK1-Mediated Mitophagy

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Ginsenoside Re (Re) was proved effective in improving depressive-like behaviors. However, the potential antidepressant mechanism of remains unrevealed. In this study, we investigated whether PINK1-mediated mitophagy and NLRP3 inflammasomes were linked to chronic unpredictable mild stress (CUMS) mice lipopolysaccharide (LPS)-stimulated astrocytes. RNA sequencing bioinformatics analyses performed discover targets pathways associated with Re. PTEN-induced putative kinase 1 (PINK1) knockdown conducted clarify role The outcomes showed that ameliorated behaviors, activated mitophagy, inhibited inflammasome activation. PINK1 attenuated effect promotion decline activation caused by reversed knockdown. conclusion, promoting exert its effect.

Language: Английский

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RTA408 alleviates lipopolysaccharide-induced acute lung injury via inhibiting Bach1-mediated ferroptosis

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113250 - 113250

Published: Sept. 27, 2024

Language: Английский

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