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

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.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.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.MKP-1 regulated microglia phenotype and inflammatory factor release in AD through modulation of the p38 signaling pathway.© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Citation

Junhua Li, Lin Wang, Qinhua Zeng, Jing He, Qing Tang, Kejian Wang, Guiqiong He. MKP-1 regulates the inflammatory activation of microglia against Alzheimer's disease. CNS neuroscience & therapeutics. 2023 Aug 21

PMID: 37602891

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