Document Type
Article
Publication Date
5-17-2024
Publication Title
Neural Regeneration Research
Abstract
JOURNAL/nrgr/04.03/01300535-202503000-00031/figure1/v/2024-06-17T092413Z/r/image-tiff Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte-derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42-induced Alzheimer's disease-like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease-like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42-induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
First Page
873
Last Page
886
PubMed ID
38886959
Volume
20
Issue
3
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Wang, Ying; Zhang, Xiang; Biverstål, Henrik; Bazan, Nicolas G.; Tan, Shuai; Li, Nailin; Ohshima, Makiko; Schultzberg, Marianne; and Li, Xiaofei, "Pro-resolving lipid mediator reduces amyloid-β42-induced gene expression in human monocyte-derived microglia" (2024). School of Medicine Faculty Publications. 2702.
https://digitalscholar.lsuhsc.edu/som_facpubs/2702
10.4103/NRR.NRR-D-23-01688