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

被引：2
作者：
Wang, Ying [1 ,2 ]
Zhang, Xiang [3 ]
Biverstal, Henrik [4 ]
Bazan, Nicolas G. [5 ]
Tan, Shuai [6 ]
Li, Nailin [6 ]
Ohshima, Makiko [1 ]
Schultzberg, Marianne [1 ]
Li, Xiaofei [1 ]
机构：
[1] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Stockholm, Sweden
[2] First Hosp Jilin Univ, Neurosci Ctr, Dept Neurol, Changchun, Jilin, Peoples R China
[3] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden
[4] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden
[5] Louisiana State Univ, Neurosci Ctr Excellence, New Orleans, LA USA
[6] Karolinska Univ Hosp, Clin Pharmacol Grp, Dept Med, Stockholm, Sweden
来源：
NEURAL REGENERATION RESEARCH | 2025年 / 20卷 / 03期
基金：
瑞典研究理事会;
关键词：
Alzheimer's disease; amyloid-beta; maresin; microglia; monocyte; neuroinflammation; resolution; RNA-sequencing; specialized pro-resolving lipid mediator; ALZHEIMERS-DISEASE; COMMON VARIANTS; INFLAMMATION; ACTIVATION; PACKAGE; ASTROCYTES; DEPOSITION; RESOLUTION; SURVIVAL; CELLS;
D O I：
10.4103/NRR.NRR-D-23-01688
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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-beta. 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-beta 42-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-beta 42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-beta 42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-beta 42 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-beta 42-induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
引用
收藏
页码：873 / 886
页数：14
相关论文
共 76 条
[1]   High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain [J].
Abelein, Axel ;
Chen, Gefei ;
Kitoka, Kristine ;
Aleksis, Rihards ;
Oleskovs, Filips ;
Sarr, Medoune ;
Landreh, Michael ;
Pahnke, Jens ;
Nordling, Kerstin ;
Kronqvist, Nina ;
Jaudzems, Kristaps ;
Rising, Anna ;
Johansson, Jan ;
Biverstal, Henrik .
SCIENTIFIC REPORTS, 2020, 10 (01)
[2]   iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases [J].
Abud, Edsel M. ;
Ramirez, Ricardo N. ;
Martinez, Eric S. ;
Healy, Luke M. ;
Nguyen, Cecilia H. H. ;
Newman, Sean A. ;
Yeromin, Andriy V. ;
Scarfone, Vanessa M. ;
Marsh, Samuel E. ;
Fimbres, Cristhian ;
Caraway, Chad A. ;
Fote, Gianna M. ;
Madany, Abdullah M. ;
Agrawal, Anshu ;
Kayed, Rakez ;
Gylys, Karen H. ;
Cahalan, Michael D. ;
Cummings, Brian J. ;
Antel, Jack P. ;
Mortazavi, Ali ;
Carson, Monica J. ;
Poon, Wayne W. ;
Blurton-Jones, Mathew .
NEURON, 2017, 94 (02) :278-+
[3]   VEGF receptor-1 modulates amyloid 1-42 oligomer-induced senescence in brain endothelial cells [J].
Angom, Ramcharan Singh ;
Wang, Ying ;
Wang, Enfeng ;
Pal, Krishnendu ;
Bhattacharya, Santanu ;
Watzlawik, Jens O. ;
Rosenberry, Terrone L. ;
Das, Pritam ;
Mukhopadhyay, Debabrata .
FASEB JOURNAL, 2019, 33 (03) :4626-4637
[4]   PPAR Regulation of Inflammatory Signaling in CNS Diseases [J].
Bright, John J. ;
Kanakasabai, Saravanan ;
Chearwae, Wanida ;
Chakraborty, Sharmistha .
PPAR RESEARCH, 2008, 2008
[5]  
Burton E., 2021, Alzheimers Dement (N Y)
[6]   Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation [J].
Colas, Romain A. ;
Dalli, Jesmond ;
Chiang, Nan ;
Vlasakov, Iliyan ;
Sanger, Julia M. ;
Riley, Ian R. ;
Serhan, Charles N. .
JOURNAL OF IMMUNOLOGY, 2016, 197 (11) :4444-4452
[7]   Microglia-Mediated Neuroprotection, TREM2, and Alzheimer's Disease: Evidence From Optical Imaging [J].
Condello, Carlo ;
Yuan, Peng ;
Grutzendler, Jaime .
BIOLOGICAL PSYCHIATRY, 2018, 83 (04) :377-387
[8]   Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia [J].
Das, Amitabh ;
Kim, Sun Hwa ;
Arifuzzaman, Sarder ;
Yoon, Taeho ;
Chai, Jin Choul ;
Lee, Young Seek ;
Park, Kyoung Sun ;
Jung, Kyoung Hwa ;
Chai, Young Gyu .
JOURNAL OF NEUROINFLAMMATION, 2016, 13
[9]   Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner [J].
Deczkowska, Aleksandra ;
Matcovitch-Natan, Orit ;
Tsitsou-Kampeli, Afroditi ;
Ben-Hamo, Sefi ;
Dvir-Szternfeld, Raz ;
Spinrad, Amit ;
Singer, Oded ;
David, Eyal ;
Winter, Deborah R. ;
Smith, Lucas K. ;
Kertser, Alexander ;
Baruch, Kuti ;
Rosenzweig, Neta ;
Terem, Anna ;
Prinz, Marco ;
Villeda, Saul ;
Citri, Ami ;
Amit, Ido ;
Schwartz, Michal .
NATURE COMMUNICATIONS, 2017, 8
[10]   Cerebrospinal Fluid Profile of Lipid Mediators in Alzheimer's Disease [J].
Do, Khanh, V ;
Hjorth, Erik ;
Wang, Ying ;
Jun, Bokkyoo ;
Kautzmann, Marie-Audrey, I ;
Ohshima, Makiko ;
Eriksdotter, Maria ;
Schultzberg, Marianne ;
Bazan, Nicolas G. .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 2023, 43 (02) :797-811
12345678