Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia-Reference-Cited by-同舟云学术

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Published:2024-05-17 Issue:3 Volume:20 Page:873-886
ISSN:1673-5374
Container-title:Neural Regeneration Research
language:en
Short-container-title:

Author:

Wang Ying¹²,Zhang Xiang³,Biverstål Henrik⁴,Bazan Nicolas G.⁵,Tan Shuai⁶,Li Nailin⁶,Ohshima Makiko¹,Schultzberg Marianne¹^ORCID,Li Xiaofei¹^ORCID

Affiliation:

1. Department of Neurobiology, Care Sciences & Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden

2. Department of Neurology, Neuroscience Center, The First Hospital of Jilin University, Changchun, Jilin Province, China

3. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

4. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

5. Neuroscience Center of Excellence, Louisiana State University, New Orleans, LA, USA

6. Department of Medicine, Solna, Clinical Pharmacology Group, Karolinska University Hospital, Stockholm, Sweden

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.

Publisher

Medknow

Reference76 articles.

1. High-yield production of amyloid-β peptide anabled by a customized spider silk domain;Abelein;Sci Rep,2020

2. iPSC-derived human microglia-like cells to study neurological diseases;Abud;Neuron,2017

3. PPAR regulation of inflammatory signaling in CNS diseases;Bright;PPAR Res,2008

4. Variant‐to‐gene mapping in human microglial cell models with CRISPR validation implicates RTFDC1 at the Alzheimer’s disease ‘CASS4’ locus;Burton;Alzheimers Dement (N Y),2021

5. Identification and actions of the maresin 1 metabolome in infectious inflammation;Colas;J Immunol,2016