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学科主题: 精神卫生
题名:
Selective filtering defect at the axon initial segment in Alzheimer′s disease mouse models
作者: Sun, Xiaqin1; Wu, Yu1; Gu, Mingxue1; Liu, Zhuo1; Ma, Yuanlin2; Li, Jun2; Zhang, Yan1
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2014-09-30
DOI: 10.1073/pnas.1411837111
卷: 111, 期:39, 页:14271-14276
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: AMYLOID-BETA ; NEURONAL POLARITY ; IN-VIVO ; PROTEIN ; PRESENILIN-1 ; TRANSPORT ; ANKYRIN(G) ; GENE ; CONTRIBUTES ; MAINTENANCE
英文摘要:

Axon pathology has been widely reported in Alzheimer′s disease (AD) patients and AD mouse models. Herein we report that increased miR-342-5p down-regulates the expression of ankyrin G (AnkG), a protein known to play a critical role in establishing selective filtering machinery at the axon initial segment (AIS). Diminished AnkG expression leads to defective AIS filtering in cultured hippocampal neurons from AD mouse models, as monitored by selective exclusion of large macromolecules from the axons. Furthermore, AnkG-deficiency impairs AIS localization of Na-v 1.6 channels and confines NR2B to the somatodendritic compartments. The expression of exogenous AnkG improved the cognitive performance of 12-mo-old APP/PS1 mice; thus, our data suggest that AnkG and impairment of AIS filtering may play important roles in AD pathology.

语种: 英语
所属项目编号: 91132718 ; 7142085
项目资助者: National Science Foundation of China ; Beijing Natural Science Foundation
WOS记录号: WOS:000342350200061
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68058
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Peking Univ, Hosp 6, Beijing 100191, Peoples R China
2.Peking Univ, PKU IDG McGovern Inst Brain Res, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China

Recommended Citation:
Sun, Xiaqin,Wu, Yu,Gu, Mingxue,et al. Selective filtering defect at the axon initial segment in Alzheimer′s disease mouse models[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(39):14271-14276.
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