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学科主题: 药学
题名:
Attenuation of neurodegenerative phenotypes in Alzheimer-like presenilin 1/presenilin 2 conditional double knockout mice by EUK1001, a promising derivative of xanomeline
作者: Wang, Dong1; Yang, Liguo1; Su, Jingjing1; Niu, Yan2; Lei, Xiaoping2; Xiong, Juan3; Cao, Xiaohua1; Hu, Yinghe1; Mei, Bing1; Hu, Jin-Feng1,3
关键词: Xanomeline ; EUK1001 ; Muscarinic M1 agonist ; Presenilins ; Neurodegeneration ; Alzheimer&prime ; s disease
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2011-07-01
DOI: 10.1016/j.bbrc.2011.05.120
卷: 410, 期:2, 页:229-234
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: MUSCARINIC RECEPTOR AGONIST ; INFLAMMATORY RESPONSES ; BEHAVIORAL SYMPTOMS ; AGED MICE ; OUT MICE ; DISEASE ; MEMORY ; ENHANCEMENT ; DEFICITS ; IMPROVES
英文摘要:

The M1/M4-preferring muscarinic agonist xanomeline was found to have some benefit in the treatment of the memory impairment of Alzheimer′s disease (AD), but side effects precluded further development. EUK1001, a fluorinated derivative of xanomeline, because of greater affinity for M1 muscarinic receptors, is likely to have a significantly better side effect profile than xanomeline. We have now studied the effects of 3-month chronic administration of EUK1001 and xanomeline (0.5 mg/kg/day) in AD-like presenilin 1/presenilin 2 conditional double knockout (PS cDKO) mice. Only EUK1001 was found to significantly ameliorate the deficit in recognition memory. Histological analysis demonstrated partial attenuation of the brain atrophy in EUK1001-treated PS cDKO mice and minimal effect in the xanomeline-treated mice. Both compounds effectively suppressed the elevation of brain tau phosphorylation in the PS cDKO mice, but neither inhibited the increased inflammatory responses. These results indicate that EUK1001 showed superiority to xanomeline with regard to attenuation of several AD-like neurodegenerative phenotypes in PS cDKO mice. These results suggest further investigation of the development of EUK1001 for the treatment of AD is indicated. (C) 2011 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 90713040 ; 30640068 ; 81070876 ; 31070993 ; 07DZ22006 ; 06DZ19002 ; 06PJ14033
项目资助者: NSFC ; STCSM
WOS记录号: WOS:000292623800013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64114
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
2.E China Normal Univ, Shanghai Key Lab Brain Funct Genom MOE & SBFG, Minist Educ, Key Lab Brain Funct Genom, Shanghai 200062, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Dong,Yang, Liguo,Su, Jingjing,et al. Attenuation of neurodegenerative phenotypes in Alzheimer-like presenilin 1/presenilin 2 conditional double knockout mice by EUK1001, a promising derivative of xanomeline[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2011,410(2):229-234.
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