Korean Black Ginseng Extract Alleviates Alzheimer’s Disease-Related Cognitive Impairment by Activating the Nrf2/HO-1 Pathway and Suppressing the p38 MAPK/NF-κB/STAT3 Pathways and NLRP3 Inflammasome via TLR2 and TLR4 Modulation

Journal of Ginseng Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Lipopolysaccharides from Porphyromonas gingivalis indirectly induce neuronal GSK3β-dependent synaptic defects and cause cognitive decline in a low-amyloid-β-concentration environment in Alzheimer's disease

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Март 20, 2025

Background Lipopolysaccharides from Porphyromonas gingivali s ( P.g LPS) are involved in the pathology of Alzheimer's disease (AD). However, effect LPS on synaptic defects remains unclear. Objective In this study, we tested our hypothesis that induces a low-amyloid-beta (Aβ)-concentration environment. Methods MG6 microglia or N2a neurons was treated with (0.1 μg/mL), soluble Aβ 42 μM) AL (combined and at 0.1 μM). Results cultured microglia, increased mRNA expression TNF-α, IL-1β IL-6 TNF-α release parallel NF-κB activation. neurons, treatment , LPS, did not affect synapsin1 (SYN1) post-synaptic density protein-95 (PSD-95). conditioned medium AL-exposed (AL-MCM) significantly reduced protein SYN1, PSD-95, nuclear translocation repressor element-1 silencing transcription factor (REST) but TNF receptor type I (at 48 h) glycogen synthase kinase (GSK)3β 24 h). TWS119 pretreatment (5 μM), GSK3β specific inhibitor, reversed AL-MCM-induced reduction SYN1 PSD-95 REST neurons. APP NL-F/NL-F mice, immunofluorescence intensity cortical positively correlated index memory test negatively TNF-α-positive microglia. Conclusions These observations demonstrate neuronal GSK3β-dependent low-Aβ concentration environment via microglial

Язык: Английский

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A predictive machine learning model for cannabinoid effect based on image detection of reactive oxygen species in microglia

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0320219 - e0320219

Опубликована: Март 25, 2025

Neuroinflammation is a key feature of human neurodisease including neuropathy and neurodegenerative disease driven by the activation microglia, immune cells nervous system. During microglia release pro-inflammatory cytokines as well reactive oxygen species (ROS) that can drive local neuronal glial damage. Phytocannabinoids are an important class naturally occurring compounds found in cannabis plant ( Cannabis sativa ) interact with body’s endocannabinoid receptor Cannabidiol (CBD) prototype phytocannabinoid anti-inflammatory properties observed animal models. We measured ROS (HMC3) using CellROX, fluorescent dynamic indicator. tested effect CBD on level presence three known activators: lipopolysaccharide (LPS), amyloid beta (A β 42 ), immunodeficiency virus (HIV) glycoprotein (GP120). Confocal microscopy images within were coupled to deep learning model convolutional neural network (CNN) predict responses. Our study demonstrates platform be used assessment image measure.

Язык: Английский

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Role of toll-like receptors in post-COVID-19 associated neurodegenerative disorders?

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Март 26, 2025

In the intricate realm of interactions between hosts and pathogens, Toll-like receptors (TLRs), which play a crucial role in innate immune response, possess ability to identify specific molecular signatures. This includes components originating from pathogens such as SARS-CoV-2, well resulting damage-associated patterns (DAMPs), endogenous molecules released after cellular damage. A developing perspective suggests that TLRs central neuroinflammation, fundamental factor neurodegenerative conditions like Alzheimer’s Parkinson’s disease (PD). comprehensive review consolidates current research investigating potential interplay TLRs, their signaling mechanisms, processes neurodegeneration following SARS-CoV-2 infection with an aim elucidate involvement long-term neurological complications COVID-19 explore targeting means implementing intervention strategies for prevention or treatment COVID-19-associated brain outcomes.

Язык: Английский

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Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Апрель 9, 2025

Язык: Английский

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NLRP1 inflammasome in neurodegenerative disorders: from pathology to therapies

Cytokine & Growth Factor Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Ethanol Induces Neuroinflammation in a Chronic Plus Binge Mouse Model of Alcohol Use Disorder via TLR4 and MyD88-Dependent Signaling

Cells, Год журнала: 2023, Номер 12(16), С. 2109 - 2109

Опубликована: Авг. 21, 2023

Ethanol induces neuroinflammation, which is believed to contribute the pathogenesis of alcohol use disorder (AUD). Toll-like receptors (TLRs) are a group pattern recognition (PRRs) expressed on both immune cells, including microglia and astrocytes, non-immune cells in central nervous system (CNS). Studies have shown that activates TLR4 signaling, resulting induction pro-inflammatory cytokines chemokines CNS. However, effect signaling pathways downstream TLR4, such as MyD88 TRIF (TICAM) has not been evaluated extensively. In current study, we treated male wild-type, TLR4-, MyD88-, TRIF-deficient mice using chronic plus binge mouse model AUD. Evaluation mRNA expression by qRT-PCR revealed ethanol increased IL-1β, TNF-α, CCL2, COX2, FosB, JunB cerebellum wild-type mice, while generally did increase these molecules TLR4- MyD88-deficient mice. Furthermore, IRF3, IRF7, IFN-β1, associated with TRIF-dependent cascade, were largely unaffected alcohol. Collectively, results suggest MyD88-dependent essential ethanol-induced neuroinflammation this

Язык: Английский

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TAX1BP1/A20 inhibited TLR2-NF-κB activation to induce tolerant expression of IL-6 in endothelial cells

International Immunopharmacology, Год журнала: 2024, Номер 139, С. 112789 - 112789

Опубликована: Июль 29, 2024

Язык: Английский

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Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation

Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16

Опубликована: Дек. 18, 2023

Microglia are crucial for brain homeostasis, and dysfunction of these cells is a key driver in most neurodegenerative diseases, including peroxisomal leukodystrophies. In X-linked adrenoleukodystrophy (X-ALD), neuroinflammatory disorder, very long-chain fatty acid (VLCFA) accumulation due to impaired degradation within peroxisomes results microglial defects, but the underlying mechanisms remain unclear. Using CRISPR/Cas9 gene editing genes VLCFA breakdown ( Abcd1, Abcd2 , Acox1 ), we recently established easily accessible BV-2 cell models study impact dysfunctional β-oxidation revealed disease-associated microglial-like signature lines. Transcriptomic analysis suggested consequences on immune response. To clarify how lipid impacts function microglia, here used RNA-sequencing functional assays related response compare wild-type mutant lines under basal conditions upon pro-inflammatory lipopolysaccharide (LPS) activation. A majority encoding proinflammatory cytokines, as well involved phagocytosis, antigen presentation, co-stimulation T lymphocytes, were found differentially overexpressed. The transcriptomic alterations reflected by altered phagocytic capacity, inflammasome activation, increased release inflammatory TNF, upregulated lymphocytes primed presenting peptides. Together, present shows that defects resulting alterations, accumulation, directly reprogram main cellular functions microglia. elucidation this link between metabolism microglia will help better understand pathogenesis

Язык: Английский

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Non-haematopoietic Sca-1+ Cells in the Retina of Adult Mice Express Functional TLR2

Stem Cell Reviews and Reports, Год журнала: 2024, Номер 20(3), С. 845 - 851

Опубликована: Янв. 6, 2024

Язык: Английский

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