MKP-1 regulates the inflammatory activation of microglia against Alzheimer's disease

IF 4.8 1区医学 Q1 NEUROSCIENCES CNS Neuroscience & Therapeutics Pub Date : 2023-08-21 DOI:10.1111/cns.14409

Junhua Li, Lin Wang, Qinhua Zeng, Jing He, Qing Tang, Kejian Wang, Guiqiong He

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Abstract

Background

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia in elderly people. Microglia-mediated neuroinflammation plays an important role in AD pathogenesis, so modulation of neuroinflammation has emerged as an essential therapeutic method to improve AD. The current study aims to investigate whether MKP-1 can regulate microglia phenotype and inflammatory factor release in AD and explore its possible mechanisms.

Methods

Amyloid precursor protein/PS1 double transgenic mice and wild-type mice were selected to study the locations of microglia and amyloid-β (Aβ) plaques in different regions of mice brains. Changes in MKP-1 of microglia were detected using AD model mice and AD model cells. Changes in phenotype and the release of inflammatory factors within immortalized BV2 murine microglia were investigated by regulating the expression of MKP-1.

Results

The distribution of microglia and Aβ plaques in the AD brain was region-specific. MKP-1 expression was downregulated in AD mice, and in vitro, with increasing Aβ concentrations, MKP-1 expression was reduced. MKP-1 over-expression increased M2 microglia but decreased M1 microglia accompanied by changes in inflammatory factors and inhibition of MKP-1 yielded the opposite result.

Conclusion

MKP-1 regulated microglia phenotype and inflammatory factor release in AD through modulation of the p38 signaling pathway.

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MKP-1 调控小胶质细胞的炎症激活，防治阿尔茨海默病

背景阿尔茨海默病（AD）是导致老年人痴呆的最常见的神经退行性疾病之一。小胶质细胞介导的神经炎症在阿尔茨海默病发病机制中起着重要作用，因此调节神经炎症已成为改善阿尔茨海默病的重要治疗方法。本研究旨在探讨MKP-1是否能调节AD的小胶质细胞表型和炎症因子释放，并探索其可能的机制。方法选择淀粉样前体蛋白/PS1双转基因小鼠和野生型小鼠，研究小胶质细胞和淀粉样蛋白-β（Aβ）斑块在小鼠大脑不同区域的位置。利用AD模型小鼠和AD模型细胞检测了小胶质细胞MKP-1的变化。通过调节 MKP-1 的表达，研究了永生化 BV2 小鼠小胶质细胞表型和炎症因子释放的变化。结果小胶质细胞和Aβ斑块在AD大脑中的分布具有区域特异性。MKP-1在AD小鼠中表达下调，在体外，随着Aβ浓度的增加，MKP-1的表达减少。MKP-1 过度表达会增加 M2 小胶质细胞，但会减少 M1 小胶质细胞，同时伴随炎症因子的变化，而抑制 MKP-1 则会产生相反的结果。结论 MKP-1 通过调节 p38 信号通路调控 AD 中的小胶质细胞表型和炎症因子释放。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.