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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Potential modulation of microglial ferroptosis by Linggui Zhugan decoction in Alzheimer's disease through IL-17 and
Peng Tang1, Danjie Zhao2, Haixia Lin2
1Department of Pharmacy, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu 610000, China.
Abstract:
Alzheimer's Disease (AD) is a neurodegenerative condition marked by cognitive decline and memory loss, with ferroptosis, an iron-dependent form of regulated cell death, emerging as a contributing factor. This study explored the potential modulatory effects of key components of the traditional Chinese medicine (TCM) formula Linggui Zhugan Decoction (LZD) on microglial ferroptosis in AD, focusing on IL-17 and TNF signaling pathways. Using single-cell RNA sequencing, we observed alterations in microglial populations and ferroptosis-related gene expression in AD mice. Network pharmacology and in vitro experiments indicated that LZD components might influence ferroptosis-related pathways, coinciding with reduced IL-17 and TNF levels in Aβ1-42-treated microglia. In vivo, LZD administration was associated with improved behavioral outcomes and modulation of ferroptosis markers. Although our findings suggest a correlation between LZD treatment and attenuation of ferroptosis-associated pathology, further mechanistic validation is necessary to establish causal links. This study provides preliminary evidence supporting the therapeutic potential of TCM in AD via inflammatory pathway modulation.
Insights
Traditional Chinese Medicine
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Alzheimer's Disease (AD) involves cognitive decline and ferroptosis.
- Microglial ferroptosis is implicated in AD pathogenesis.
- Interleukin-17 (IL-17) and Tumor Necrosis Factor (TNF) signaling pathways are relevant.
Purpose of the Study:
- To investigate the effects of Linggui Zhugan Decoction (LZD) on microglial ferroptosis in AD.
- To explore the role of IL-17 and TNF signaling pathways in LZD's modulation of ferroptosis.
- To assess LZD's therapeutic potential in an AD mouse model.
Main Methods:
- Single-cell RNA sequencing in AD mice.
- Network pharmacology analysis.
- In vitro experiments with Aβ1-42-treated microglia.
- In vivo behavioral tests and ferroptosis marker analysis.
Main Results:
- LZD components potentially modulate ferroptosis-related pathways.
- LZD treatment reduced IL-17 and TNF levels in microglia.
- In vivo administration of LZD improved behavioral outcomes and modulated ferroptosis markers.
- Alterations in microglial populations and ferroptosis gene expression were observed in AD mice.
Conclusions:
- LZD shows potential in attenuating ferroptosis-associated pathology in AD.
- Modulation of inflammatory pathways (IL-17, TNF) may underlie LZD's effects.
- Further research is needed to confirm causal mechanisms of LZD in AD treatment.
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