Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model

被引：146
|
作者：
Zhang, Yongfang [2 ]
Kurup, Pradeep [2 ]
Xu, Jian [2 ]
Carty, Nikisha [2 ]
Fernandez, Stephanie M. [2 ]
Nygaard, Haakon B. [3 ,4 ]
Pittenger, Christopher [5 ]
Greengard, Paul [1 ]
Strittmatter, Stephen M. [3 ,4 ,6 ]
Nairn, Angus C. [5 ]
Lombroso, Paul J. [2 ,5 ,6 ]
机构：
[1] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA
[2] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA
[4] Yale Univ, Dept Neurol, Sch Med, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA
[6] Yale Univ, Dept Neurobiol, Sch Med, New Haven, CT 06520 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 44期
基金：
美国国家卫生研究院;
关键词：
beta amyloid; glutamate receptor trafficking; protein tyrosine phosphatase; long-term potentiation; LONG-TERM POTENTIATION; IMPAIR SYNAPTIC PLASTICITY; NMDA RECEPTOR TRAFFICKING; AMYLOID-BETA; A-BETA; TRANSGENIC MICE; OLIGOMERS; MEMORY; FYN; ACTIVATION;
D O I：
10.1073/pnas.1013543107
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder. Early in the pathophysiology of AD, synaptic function is disrupted by soluble A beta oligomers, possibly through A beta-mediated internalization of NMDA receptors. Striatal-enriched phosphatase (STEP) is a tyrosine phosphatase that regulates the internalization of NMDA receptors. Recent work shows that STEP is elevated in the prefrontal cortex of human AD patients and in animal models of AD. Here, we use genetic manipulations to reduce STEP activity in a triple transgenic AD mouse model and show that a decrease in STEP levels reverses cognitive and cellular deficits observed in these mice. Our results suggest that STEP inhibitors may prove therapeutic for this devastating disorder.
引用
收藏
页码：19014 / 19019
页数：6
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