LRP1 is a master regulator of tau uptake and spread

doi:10.1038/s41586-020-2156-5

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2156-5
	LRP1 is a master regulator of tau uptake and spread
	Han, Yan 1; Reyes, Alexis A.1,2; Malik, Sara 1; He, Yuan 1,2,3,4
	2020-03-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	580 期号:7803 页码:381-+
文章类型	Article
语种	英语
国家	USA; Germany
英文关键词	The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis of several forms of dementia known as tauopathies-including Alzheimer' s disease, frontotemporal dementia and chronic traumatic encephalopathy(1). Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity(2). This observation and complementary experimental studies(3,4) have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000530151300031
WOS关键词	RECEPTOR-RELATED PROTEIN-1 ; HEPARAN-SULFATE PROTEOGLYCAN ; HUMAN NEURONS ; MOUSE MODEL ; PROPAGATION ; NEURODEGENERATION ; PATHOLOGY ; BINDING ; APOE ; RAP
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281213
专题	地球科学资源环境科学气候变化
作者单位	1.Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA; 2.Northwestern Univ, Interdisciplinary Biol Sci Program, Evanston, IL 60208 USA; 3.Northwestern Univ, Chem Life Proc Inst, Evanston, IL 60208 USA; 4.Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
推荐引用方式 GB/T 7714	Han, Yan,Reyes, Alexis A.,Malik, Sara,et al. LRP1 is a master regulator of tau uptake and spread[J]. NATURE,2020,580(7803):381-+.
APA	Han, Yan,Reyes, Alexis A.,Malik, Sara,&He, Yuan.(2020).LRP1 is a master regulator of tau uptake and spread.NATURE,580(7803),381-+.
MLA	Han, Yan,et al."LRP1 is a master regulator of tau uptake and spread".NATURE 580.7803(2020):381-+.