Egln3 expression in microglia enhances the neuroinflammatory responses in Alzheimer's disease.

Abstract

Alzheimer's disease (AD), characterized by cognitive and behavioral abnormalities, is the most prevalent neurodegenerative disease worldwide. Neuroinflammation, which is induced by microglial activation, resulting in the expression of a multitude of inflammatory factors, is one of the principal characteristics of AD. Herein, we found that Egln3 is differentially expressed in microglia in the brains of AD mice. Egln3 is a member of the Egln family of proline hydroxylases, which regulates a variety of biological processes, including transcription, the cell cycle, and apoptosis, through hydroxylation, ubiquitylation, and participation in glycolysis. To further observe the effects of Egln3 on cognitive function, we utilized APP/PS1 mice as a pathological model of AD to conduct behavioral experiments and assess the expression levels of Aβ and inflammatory factors. The specific mechanisms by which Egln3 affects microglial activation were analyzed using in vitro experiments and transcriptome sequencing. The results of these analyses demonstrated that Egln3 is highly expressed in microglia in AD. Inhibition of Egln3 expression in the brains of APP/PS1 mice improves neuroinflammatory responses and cognitive function, indicating that a high expression of Egln3 promotes AD progression. Furthermore, our findings indicate that Egln3 could activate the MAPK pathway, which in turn contributes to the aggravation of neuroinflammation. Inhibition of the MAPK pathway results in attenuation of the pro-inflammatory state of microglia. Consequently, Egln3 may exacerbate neuroinflammation and promote AD progression via the MAPK pathway in microglia, making it a promising target for AD-related therapies.