| Literature DB >> 30189209 |
Bahareh Eftekharzadeh1, J Gavin Daigle2, Larisa E Kapinos3, Alyssa Coyne2, Julia Schiantarelli1, Yari Carlomagno4, Casey Cook4, Sean J Miller2, Simon Dujardin1, Ana S Amaral1, Jonathan C Grima2, Rachel E Bennett1, Katharina Tepper1, Michael DeTure5, Charles R Vanderburg1, Bianca T Corjuc1, Sarah L DeVos1, Jose Antonio Gonzalez1, Jeannie Chew2, Svetlana Vidensky2, Fred H Gage6, Jerome Mertens6, Juan Troncoso5, Eckhard Mandelkow7, Xavier Salvatella8, Roderick Y H Lim3, Leonard Petrucelli4, Susanne Wegmann1, Jeffrey D Rothstein9, Bradley T Hyman10.
Abstract
Tau is the major constituent of neurofibrillary tangles in Alzheimer's disease (AD), but the mechanism underlying tau-associated neural damage remains unclear. Here, we show that tau can directly interact with nucleoporins of the nuclear pore complex (NPC) and affect their structural and functional integrity. Pathological tau impairs nuclear import and export in tau-overexpressing transgenic mice and in human AD brain tissue. Furthermore, the nucleoporin Nup98 accumulates in the cell bodies of some tangle-bearing neurons and can facilitate tau aggregation in vitro. These data support the hypothesis that tau can directly interact with NPC components, leading to their mislocalization and consequent disruption of NPC function. This raises the possibility that NPC dysfunction contributes to tau-induced neurotoxicity in AD and tauopathies.Entities:
Keywords: Alzheimer’s disease; Nup98; nuclear pore complex; nucleocytoplasmic transport; tauopathies
Mesh：
Substances：
Year: 2018 PMID： 30189209 PMCID： PMC6240334 DOI： 10.1016/j.neuron.2018.07.039
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173