Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer's Disease.
Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer's Disease.
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DOI：
10.1016/j.neuron.2018.07.039
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发表时间：
2018-09-05
期刊：
影响因子：
16.2
通讯作者：
Hyman BT
中科院分区：
文献类型：
--
作者：
Eftekharzadeh B;Daigle JG;Kapinos LE;Coyne A;Schiantarelli J;Carlomagno Y;Cook C;Miller SJ;Dujardin S;Amaral AS;Grima JC;Bennett RE;Tepper K;DeTure M;Vanderburg CR;Corjuc BT;DeVos SL;Gonzalez JA;Chew J;Vidensky S;Gage FH;Mertens J;Troncoso J;Mandelkow E;Salvatella X;Lim RYH;Petrucelli L;Wegmann S;Rothstein JD;Hyman BT
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 tauoverexpressing 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. Nuclear pore complexes control trafficking of proteins and RNA in and out of the nucleus. These studies now provide evidence that AD related tau disrupts nuclear pore function in Alzheimer’s disease and that nuclear pore proteins cause tau to aggregate.
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影响因子：
25
作者：
Chou CC;Zhang Y;Umoh ME;Vaughan SW;Lorenzini I;Liu F;Sayegh M;Donlin-Asp PG;Chen YH;Duong DM;Seyfried NT;Powers MA;Kukar T;Hales CM;Gearing M;Cairns NJ;Boylan KB;Dickson DW;Rademakers R;Zhang YJ;Petrucelli L;Sattler R;Zarnescu DC;Glass JD;Rossoll W
通讯作者：
Rossoll W
影响因子：
16.2
作者：
Hoover, Brian R.;Reed, Miranda N.;Su, Jianjun;Penrod, Rachel D.;Kotilinek, Linda A.;Grant, Marianne K.;Pitstick, Rose;Carlson, George A.;Lanier, Lorene M.;Yuan, Li-Lian;Ashe, Karen H.;Liao, Dezhi
通讯作者：
Liao, Dezhi
DOI：
10.1097/nen.0b013e3181609361
发表时间：
2008-01-01
影响因子：
3.2
作者：
Freeman, Stefanie H.;Spires-Jones, Tara;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.
影响因子：
4.8
作者：
Blevins, MB;Smith, AM;Powers, MA
通讯作者：
Powers, MA
影响因子：
9.8
作者：
Dasso, M;Pu, RT
通讯作者：
Pu, RT