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

页码：1101 / 1104

页数：4

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