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

作者全名："Li, Junhua; Wang, Lin; Zeng, Qinhua; He, Jing; Tang, Qing; Wang, Kejian; He, Guiqiong"

作者地址："[Li, Junhua; Zeng, Qinhua; He, Jing; Tang, Qing; Wang, Kejian; He, Guiqiong] Chongqing Med Univ, Inst Neurosci, Basic Med Coll, Chongqing, Peoples R China; [Li, Junhua; Zeng, Qinhua; He, Jing; Tang, Qing; Wang, Kejian; He, Guiqiong] Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing 400016, Peoples R China; [Wang, Lin] Chongqing Coll Tradit Chinese Med, Dept Basic Med, Chongqing, Peoples R China"

通信作者："Wang, KJ; He, GQ (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing 400016, Peoples R China."

来源：CNS NEUROSCIENCE & THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001051406400001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Alzheimer's disease; microglia; MKP-1; neuroinflammation

摘要："BackgroundAlzheimer'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. MethodsAmyloid precursor protein/PS1 double transgenic mice and wild-type mice were selected to study the locations of microglia and amyloid-& beta; (A & beta;) 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. ResultsThe distribution of microglia and A & beta; plaques in the AD brain was region-specific. MKP-1 expression was downregulated in AD mice, and in vitro, with increasing A & beta; 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. ConclusionMKP-1 regulated microglia phenotype and inflammatory factor release in AD through modulation of the p38 signaling pathway."

基金机构："CQMU Program for Youth Innovation in Future Medicine [W0044]; General project of Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0442]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJCXZD2020021, KJZD-K201900403]"

基金资助正文："CQMU Program for Youth Innovation in Future Medicine, Grant/Award Number: W0044; General project of Chongqing Natural Science Foundation, Grant/Award Number: cstc2021jcyj-msxmX0442; the Scientific and Technological Research Program of Chongqing Municipal Education Commission, Grant/Award Number: KJCXZD2020021 and KJZD-K201900403"