Treponema pallidum Flagellin FlaB3 Activates Inflammation and Inhibits Autophagy in HMC3 Cells via the TLR4 Pathway

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Neurosyphilis, a neurological manifestation of syphilis, is closely related to neuroinflammation. Autophagy, fundamental cellular mechanism that mediates the degradation intracellular components, plays crucial role in immune regulation and inflammation. Microglia, resident cells brain, are central these processes. However, interplay between autophagy neuroinflammation context neurosyphilis remains poorly understood. In this research, recombinant Treponema pallidum flagellin, FlaB3, was constructed treat human microglia clone 3 (HMC3) HMC3 which TLR4 (Toll-like receptor 4) had been knocked down. We discovered FlaB3 promotes IL-6 IL-8 secretion through pathway. also observed regulates expression autophagy-related proteins Beclin1, LC3B, P62 via TLR4/PI3K/AKT/mTOR pathway, thereby inhibiting autophagic flux cells. Subsequently, we concentration soluble amyloid β1-42 (Aβ1-42) decreased cerebrospinal fluid patients. Immunofluorescence analysis further revealed suppresses Aβ by autophagosomes Additionally, treatment with activators Rapamycin LY294002 levels secretion, indicating modulates inflammation summary, our study demonstrates autophagy. This inhibition impedes degradation, providing new insights into pathogenesis neurosyphilis.

Language: Английский

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TREM2 Impedes Recovery After Spinal Cord Injury by Regulating Microglial Lysosomal Membrane Permeabilization‐Mediated Autophagy

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: May 4, 2025

ABSTRACT Microglia, considered as the main immune responder, play an important role in regulating neuroinflammation central nervous system (CNS) disorders. Our previous work found that TREM2 is highly expressed microglia and related to their functional state. However, specific of spinal cord injury has not yet been explored. To further investigate potential mechanism TREM2, we performed single‐cell sequencing on wild‐type (Wt) Trem2 −/− mice before after injury. Compared Wt mice, lysosome, autophagy membrane‐related pathways are more strongly activated suggesting may exert its effects by influencing lysosomal membranes autophagy. Mechanistically, demonstrated knockout can reduce nuclear translocation TFEB decreasing phosphorylation Syk. Furthermore, validated vitro vivo silencing promote repairing membrane permeabilization. Through immunofluorescence, 3D gait analysis, motor evoked experiments, H&E staining Masson staining, increased level rescue both histological recovery Collectively, these results only suggest microglial regulated a TREM2‐dependent LMP manner, but also, importantly, they provide promising clinical translation strategy based gene therapy for lysosome‐related

Language: Английский

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Artemisiae Iwayomogii Herba Protects Dopaminergic Neurons Against 1-Methyl-4-phenylpyridinium/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Neurotoxicity in Models of Parkinson’s Disease

Nutrients, Journal Year: 2025, Volume and Issue: 17(10), P. 1672 - 1672

Published: May 14, 2025

Background/Objectives: Parkinson’s disease (PD) is a common neurodegenerative characterized by motor symptoms caused the loss of dopaminergic neurons. While pathophysiology PD still not fully understood, it recognized that oxidative stress plays major role in its progression. Previous studies have shown aerial parts Artemisia iwayomogi Kitamura (AIK) possess medicinal properties, including antioxidant activity. This study aimed to investigate whether AIK can alleviate neuronal and model explore therapeutic mechanisms. Methods: For vitro study, PC12 cells were treated with 1-methyl-4-phenylpyridinium (MPP+). vivo C57BL/6J mice orally administered for 12 days; they received intraperitoneal injections 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 5 consecutive days, starting on 8th day administration. Results: treatment presence MPP+ enhanced phosphorylation protein kinase B/glycogen synthase kinase-3β signaling pathway, which crucial regulator nuclear factor erythroid 2-related 2 (Nrf2) translocation. Additionally, increased cell survival induced an response involving heme oxygenase-1, via increasing level Nrf2 nucleus. In MPTP-induced mouse PD, administration activated neurons prevented brain, turn alleviated dysfunction. Conclusions: Collectively, these findings suggest potential botanical candidate protecting through

Language: Английский

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Ginsenoside C-K Inhibits Aβ Oligomer-Induced Alzheimer's Disease Pathology Progression by Regulating Microglia-Neuron Interactions

IBRO Neuroscience Reports, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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