气候变化领域集成服务门户(CCPortal): A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis

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DOI	10.1073/PNAS.2025102118
	A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis
	Mifflin L.; Hu Z.; Dufort C.; Hession C.C.; Walker A.J.; Niu K.; Zhu H.; Liu N.; Liu J.S.; Levin J.Z.; Stevens B.; Yuan J.; Zou C.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Microglial-derived inflammation has been linked to a broad range of neurodegenerative and neuropsychiatric conditions, including amyotrophic lateral sclerosis (ALS). Using single-cell RNA sequencing, a class of Disease-Associated Microglia (DAMs) have been characterized in neurodegeneration. However, the DAM phenotype alone is insufficient to explain the functional complexity of microglia, particularly with regard to regulating inflammation that is a hallmark of many neurodegenerative diseases. Here, we identify a subclass of microglia in mouse models of ALS which we term RIPK1-Regulated Inflammatory Microglia (RRIMs). RRIMs show significant up-regulation of classical proinflammatory pathways, including increased levels of Tnf and Il1b RNA and protein. We find that RRIMs are highly regulated by TNFα signaling and that the prevalence of these microglia can be suppressed by inhibiting receptor-interacting protein kinase 1 (RIPK1) activity downstream of the TNF receptor 1. These findings help to elucidate a mechanism by which RIPK1 kinase inhibition has been shown to provide therapeutic benefit in mouse models of ALS and may provide an additional biomarker for analysis in ongoing phase 2 clinical trials of RIPK1 inhibitors in ALS. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ALS; Microglia; Neuroinflammation; RIPK1; ScRNAseq
语种	英语
scopus关键词	cell enzyme; receptor interacting protein kinase 1; tumor necrosis factor; unclassified drug; adult; amyotrophic lateral sclerosis; animal experiment; animal model; animal tissue; Article; controlled study; downstream processing; enzyme inhibition; male; microglia; mouse; nervous system inflammation; nonhuman; prevalence; priority journal; RNA sequencing; signal transduction; upregulation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180046
作者单位	Department of Cell Biology, Harvard Medical School, Boston, MA 02115, United States; Department of Statistics, Harvard University, Cambridge, MA 02138, United States; F. M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, United States; Stanley Center for Psychiatric Research, Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201203, China
推荐引用方式 GB/T 7714	Mifflin L.,Hu Z.,Dufort C.,et al. A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis[J],2021,118(13).
APA	Mifflin L..,Hu Z..,Dufort C..,Hession C.C..,Walker A.J..,...&Zou C..(2021).A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Mifflin L.,et al."A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).