Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death

被引：74

作者：

d'Abramo, C

Massone, S

Zingg, JM

Pizzuti, A

Marambaud, P

Dalla Piccola, B

Azzi, A

Marinari, UM

Pronzato, MA

Ricciarelli, R ^{[1
]}

机构：

[1] Univ Genoa, Dept Expt Med, I-16132 Genoa, Italy

[2] Univ Bern, Inst Biochem & Mol Biol, CH-3012 Bern, Switzerland

[3] Univ Roma La Sapienza, Inst Med, I-00198 Rome, Italy

[4] IRCCS, Casa Sollievo Sofferenza, I-00198 Rome, Italy

[5] N Shore LIJ Res Inst, New York, NY 11030 USA

来源：

BIOCHEMICAL JOURNAL | 2005年 / 391卷

关键词：

Alzheimer's disease; non-steroidal anti-inflammatory drugs (NSAIDs); peroxisome proliferator-activated receptor gamma (PPAR gamma); amyloid-beta; amyloid precursor protein (APP);

D O I：

10.1042/BJ20050560

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 data indicate that PPAR gamma (peroxisome proliferator-activated receptor gamma) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. In the present study we show that PPAR gamma overexpression in cultured cells dramatically reduced A beta (amyloid-beta) secretion, affecting the expression of the APP (A beta precursor protein) at a post-transcriptional level. APP down-regulation did not involve the pathway of the secretases, and correlated with a significant induction of APP ubiquitination. Additionally, we demonstrate that PPAR gamma was able to protect the cells from H2O2-induced necrosis by decreasing A beta secretion. Taken together, our results indicate a novel mechanism at the basis of the neuroprotection shown by PPAR gamma agonists and an additional pathogenic role for A beta accumulation.

引用

页码：693 / 698

页数：6

共 27 条

[1] Inhibitors of β-amyloid formation based on the β-secretase cleavage site [J].

Abbenante, G ;

Kovacs, DM ;

Leung, DL ;

Craik, DJ ;

Tanzi, RE ;

Fairlie, DP .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 268 (01) :133-135

[2] Inflammation and Alzheimer's disease [J].

Akiyama, H ;

Barger, S ;

Barnum, S ;

Bradt, B ;

Bauer, J ;

Cole, GM ;

Cooper, NR ;

Eikelenboom, P ;

Emmerling, M ;

Fiebich, BL ;

Finch, CE ;

Frautschy, S ;

Griffin, WST ;

Hampel, H ;

Hull, M ;

Landreth, G ;

Lue, LF ;

Mrak, R ;

Mackenzie, IR ;

McGeer, PL ;

O'Banion, MK ;

Pachter, J ;

Pasinetti, G ;

Plata-Salaman, C ;

Rogers, J ;

Rydel, R ;

Shen, Y ;

Streit, W ;

Strohmeyer, R ;

Tooyoma, I ;

Van Muiswinkel, FL ;

Veerhuis, R ;

Walker, D ;

Webster, S ;

Wegrzyniak, B ;

Wenk, G ;

Wyss-Coray, T .

NEUROBIOLOGY OF AGING, 2000, 21 (03) :383-421

[3] Peroxisome proliferator-activated receptor γ induces a clearance mechanism for the amyloid-β peptide [J].

Camacho, IE ;

Serneels, L ;

Spittaels, K ;

Merchiers, P ;

Dominguez, D ;

De Strooper, B .

JOURNAL OF NEUROSCIENCE, 2004, 24 (48) :10908-10917

[4] Role of the proteasome in Alzheimer's disease [J].

Checler, F ;

da Costa, CA ;

Ancolio, K ;

Chevallier, N ;

Lopez-Perez, E ;

Marambaud, P .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2000, 1502 (01) :133-138

[5] Inflammatory mechanisms in Alzheimer's disease:: Inhibition of β-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARγ agonists [J].

Combs, CK ;

Johnson, DE ;

Karlo, JC ;

Cannady, SB ;

Landreth, GE .

JOURNAL OF NEUROSCIENCE, 2000, 20 (02) :558-567

[6] NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo [J].

Eriksen, JL ;

Sagi, SA ;

Smith, TE ;

Weggen, S ;

Das, P ;

McLendon, DC ;

Ozols, VV ;

Jessing, KW ;

Zavitz, KH ;

Koo, EH ;

Golde, TE .

JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (03) :440-449

[7] Proteasome-mediated effects on amyloid precursor protein processing at the γ-secretase site [J].

Flood, F ;

Murphy, S ;

Cowburn, RF ;

Lannfelt, L ;

Walker, B ;

Johnston, JA .

BIOCHEMICAL JOURNAL, 2005, 385 :545-550

[8] Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease [J].

in 't Veld, BA ;

Ruitenberg, A ;

Hofman, A ;

Launer, LJ ;

van Duijn, CM ;

Stijnen, T ;

Breteler, MMB ;

Stricker, BHC .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (21) :1515-1521

[9] DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements - Importance of the 5'-flanking region [J].

JugeAubry, C ;

Pernin, A ;

Favez, T ;

Burger, AG ;

Wahli, W ;

Meier, CA ;

Desvergne, B .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (40) :25252-25259

[10] Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice [J].

Lim, GP ;

Yang, F ;

Chu, T ;

Gahtan, E ;

Ubeda, O ;

Beech, W ;

Overmier, JB ;

Hsiao-Ashe, K ;

Frautschy, SA ;

Cole, GM .

NEUROBIOLOGY OF AGING, 2001, 22 (06) :983-991

← 1 2 3 →