Antagonist of peroxisome proliferator-activated receptor γ induces cerebellar amyloid-β levels and motor dysfunction in APP/PS1 transgenic mice

被引：22

作者：

Du, Jing ^{[1
]}

Sun, Bing ^{[1
]}

Chen, Kui ^{[2
]}

Fan, Li ^{[2
,3
]}

Wang, Zhao ^{[1
]}

机构：

[1] Tsinghua Univ, Prot Sci Key Lab, Minist Educ, Dept Biol Sci & Biotechnol,Sch Med, Beijing 100084, Peoples R China

[2] Anhui Med Univ, Dept Pharmacol, Hefei 230032, Anhui, Peoples R China

[3] Providence Heart & Vasc Inst, Cardiovasc Res Starr Acad Ctr, Portland, OR 97225 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 384卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Peroxisome poliferator-activated receptor gamma; Amyloid-beta; Cerebellum; Cerebellar dysfunction; GW9662; Insulin-degrading enzyme; Alzheimer's disease; ALZHEIMERS-DISEASE; MOUSE MODEL; MEMORY; ASSOCIATION; DEFICITS; INSULIN;

D O I：

10.1016/j.bbrc.2009.04.148

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent evidences show that peroxisome proliferator-activated receptor gamma (PPAR gamma) is involved in the modulation of the amyloid-beta (A beta) cascade causing Alzheimer's disease (AD) and treatment with PPAR gamma agonists protects against AD pathology. However, the function of PPARs gamma, steady-state activity in A beta cascade and AD pathology remains unclear. In this study, an antagonist of PPAR gamma, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPAR gamma activity in cerebellum. The results show that inhibition of PPAR gamma significantly induced A beta levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of A beta. Since cerebellum is spared front significant A beta accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPAR gamma steady-state activity in protection of cerebellum against AD pathology. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：357 / 361

页数：5

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