Suspected limited efficacy of γ-secretase modulators

被引：10
|
作者：
Kakuda, Nobuto [1 ,2 ]
Akazawa, Kohei [3 ]
Hatsuta, Hiroyuki [4 ]
Murayama, Shigeo [4 ]
Ihara, Yasuo [1 ,2 ,5 ,6 ]
机构：
[1] Doshisha Univ, Fac Life & Med Sci, Dept Neuropathol, Kyoto 602, Japan
[2] Japan Sci & Technol Agcy, CREST, Saitama, Japan
[3] Niigata Univ, Med & Dent Hosp, Dept Med Informat, Niigata, Japan
[4] Tokyo Metropolitan Inst Gerontol, Dept Neuropathol, Tokyo, Japan
[5] Doshisha Univ, Ctr Neurol Dis, Kyoto 602, Japan
[6] New Energy & Ind Technol Dev Org NEDO, Kanagawa, Japan
来源：
NEUROBIOLOGY OF AGING | 2013年 / 34卷 / 04期
关键词：
gamma-Secretase; gamma-Modulator; Alzheimer's disease; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; A-BETA; TRANSMEMBRANE DOMAIN; PRESENILINS; PROTEIN; TARGET;
D O I：
10.1016/j.neurobiolaging.2012.08.017
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
Mild cognitive impairment and Alzheimer's disease (AD) are associated with changes in gamma-secretase activity in the brain, producing an amyloid beta-protein-42-lowering gamma-modulator-like effect. We show here that this modulation occurs at the stage of amyloid deposition, presumably decades earlier than the onset of AD. In addition, gamma-secretase modulator-1, a gamma-modulator, altered gamma-secretase activity in the AD brain but to a lesser extent than in the normal brain. These findings suggest that gamma-modulators have limited efficacy against amyloid deposition and AD. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码：1101 / 1104
页数：4
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