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Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing 期刊论文

编号：

e1052326-71fb-4bad-8bd6-2fa01dfc7a58
作者：

Hu, Tao#^[1,2]Xiao, Zhangang#^[3,4]Mao, Rui(毛瑞)#^[5]Chen, Bo(陈波)#^[6]Lu, MinNan(卢敏南)#^[6]Tong, Jun(佟钧)#^[7]Mei, Rong^[8];Li, ShanShan^[9];Xiao, ZhiCheng(肖志成)^[10,11]Zhang, LianFeng^[12,13];Xiyang, YanBin(习杨彦彬)*^[1]
语种：

英文
期刊：

ONCOTARGET ISSN：1949-2553 2017 年 8 卷 59 期 (99284 - 99295) ; NOV 21
收录：
关键词：

voltage-gated sodium channels beta 2 Alzheimer's disease APP/PS1 mouse neuronal activity cognition Gerotarget
摘要：

Voltage-gated sodium channels beta 2 (Nav beta 2, encoded by SCN2B) is a substrate of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and regulates cell surface expression of channels in neurons. Previous studies reported enhanced Nav beta 2 processing by BACE1 in Alzheimer's disease (AD) model and patients. We investigated whether changes in Nav beta 2 expression affect neuronal seizure and amyloid precursor protein (APP) processing in an AD mouse model. Our study used eight-month-old APP/presenilin 1 (PS1) mice and transgenic Nav beta 2 knockdown [by 61% vs. wild type (WT)] APP/PS1 mice (APP/PS1/Nav beta 2-kd), with age-matched WT and Nav beta 2 knockdown (Nav beta 2-kd) mice as controls. We found that Nav beta 2 knockdown in APP/PS1 mice partially reversed the abnormal Nav beta 2 cleavage and the changes in intracellular and total Nav1.1 alpha expression. It also restored sodium currents density in hippocampal neurons and neuronal activity, as indicated by EEG tracing; improved Morris water maze performance; and shifted APP amyloidogenic metabolism towards non-amyloidogenic processing. There were no differences in these indicators between WT and Nav beta 2-kd mice. These results suggest Nav beta 2 knockdown may be a promising strategy for treating AD.
推荐引用方式
GB/T 7714：

Hu Tao,Xiao Zhangang,Mao Rui, et al. Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing [J].ONCOTARGET,2017,8(59):99284-99295.
APA：

Hu Tao,Xiao Zhangang,Mao Rui,Chen Bo,&Xiyang Yan-Bin.(2017).Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing .ONCOTARGET,8(59):99284-99295.
MLA：

Hu Tao, et al. "Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing" .ONCOTARGET 8,59(2017):99284-99295.
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