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LRP1 is a master regulator of tau uptake and spread 期刊论文
NATURE, 2020, 580 (7803) : 381-+
作者:  Han, Yan;  Reyes, Alexis A.;  Malik, Sara;  He, Yuan
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

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.


  
Evaluating maximum stand density and size-density relationships based on the Competition Density Rule in Korean pines and Japanese larch 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2019, 446: 204-213
作者:  Lee, Daesung;  Choi, Jungkee
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Maximum stem number  Carrying capacity  Self-thinning  Tree mortality  Stand density index  
Land use and socio-economic determinants of urban forest structure and diversity 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 181: 10-21
作者:  Fan, Chao;  Johnston, Mark;  Darling, Lindsay;  Scott, Lydia;  Liao, Felix Haifeng
收藏  |  浏览/下载:7/0  |  提交时间:2019/04/09
Urban forests  Stem density  Species diversity  Land use  Socio-economic  Social inequality  
The effect of thinning on structural attributes of a low rainfall forest in eastern Australia 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2018, 409: 571-583
作者:  Waters, Cathleen M.;  Gonsalves, Leroy;  Law, Bradley;  Melville, Gavin;  Toole, Ian;  Brassil, Traecey;  Tap, Patrick
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Chronosequence  Biodiversity  Restoration  Cypress  Coarse woody debris  Stem density  
Abundance, population structure and harvesting selection of two palm species (Hyphaene coriacea and Phoenix reclinata) in Zitundo area, southern Mozambique 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2017, 398
作者:  Martins, Angelina R. O.;  Shackleton, Charlie M.
收藏  |  浏览/下载:4/0  |  提交时间:2019/04/09
Cluster density  Preference ratio  Size distribution  Stability indices  Stem density  Tapping