Efficient Four-Drug Cocktail Therapy Targeting Amyloid-β Peptide for Alzheimer's Disease

被引：15

作者：

Asai, Masashi ^{[1
,2
]}

Iwata, Nobuhisa ^{[2
]}

Tomita, Taisuke ^{[3
,4
]}

Iwatsubo, Takeshi ^{[3
,4
,5
]}

Ishiura, Shoichi ^{[6
]}

Saido, Takaomi C. ^{[2
]}

Maruyama, Kei ^{[1
]}

机构：

[1] Saitama Med Univ, Fac Med, Dept Pharmacol, Saitama, Japan

[2] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Saitama, Japan

[3] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Tokyo, Japan

[4] Japan Sci & Technol Corp, CREST, Tokyo, Japan

[5] Univ Tokyo, Grad Sch Med, Dept Neuropathol, Tokyo, Japan

[6] Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Tokyo, Japan

来源：

JOURNAL OF NEUROSCIENCE RESEARCH | 2010年 / 88卷 / 16期

基金：

日本学术振兴会;

关键词：

NSAID; beta-secretase inhibitor; gamma-secretase inhibitor; statin; cocktail therapy; GAMMA-SECRETASE INHIBITOR; A-BETA; IN-VIVO; PRECURSOR PROTEIN; NSAIDS; A-BETA-42; PATHOLOGY; METABOLISM; PREVENTION; A-BETA(42);

D O I：

10.1002/jnr.22503

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Cocktail treatment is an effective multidrug medication therapy for some diseases, such as cancer and AIDS, because of the additive or synergistic effect of each medicine and relief from adverse effects. Amyloid-beta peptide (A beta), which is now recognized as central to the development of Alzheimer's disease (AD), is derived from the sequential proteolysis of amyloid precursor protein (APP) by beta- and gamma-secretases. Secretase inhibitors are one of most attractive targets for therapeutic intervention in AD. However, because beta- and gamma-secretases cleave not only APP but also other substrate proteins, strong inhibition of these secretases leads to severe adverse effects. Some nonsteroidal antiinflammatory drugs (NSAIDs) and cholesterol-lowering drugs (statins) can modify the production of A beta. Here, we report that a cocktail treatment with four drugs (NSAID, statin, and beta- and gamma-secretase inhibitors) had additive effects on the reduction of A beta levels in cultured cells without competing with each other. Moreover, the four-drug cocktail treatment caused no changes in processing of the gamma-secretase substrate Notch. This is suggests that this cocktail treatment could be a new therapeutic approach for AD. (C) 2010 Wiley-Liss, Inc.

引用

页码：3588 / 3597

页数：10

共 43 条

[1]

The novel β-secretase inhibitor KMI-429 reduces amyloid β peptide production in amyloid precursor protein transgenic and wild-type mice [J].

Asai, M ;

Hattori, C ;

Iwata, N ;

Saido, TC ;

Sasagawa, N ;

Szabó, B ;

Hashimoto, Y ;

Maruyama, K ;

Tanuma, S ;

Kiso, Y ;

Ishiura, S .

JOURNAL OF NEUROCHEMISTRY, 2006, 96 (02) :533-540

[2]

Berberine alters the processing of Alzheimer's amyloid precursor protein to decrease Aβ secretion [J].

Asai, Masashi ;

Iwata, Nobuhisa ;

Yoshikawa, Ayumu ;

Aizaki, Yoshimi ;

Ishiura, Shoichi ;

Saido, Takaomi C. ;

Maruyama, Kei .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 352 (02) :498-502

[3]

Substrate specificity of γ-secretase and other intramembrane proteases [J].

Beel, A. J. ;

Sanders, C. R. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (09) :1311-1334

[4]

Pharmacological knock-down of the presenilin 1 heterodimer by a novel γ-secretase inhibitor -: Implications for presenilin biology [J].

Beher, D ;

Wrigley, JDJ ;

Nadin, A ;

Evin, G ;

Masters, CL ;

Harrison, T ;

Castro, JL ;

Shearman, MS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (48) :45394-45402

[5]

Alzheimer's disease [J].

Scheltens, Philip ;

De Strooper, Bart ;

Kivipelto, Miia ;

Holstege, Henne ;

Chetelat, Gael ;

Teunissen, Charlotte E. ;

Cummings, Jeffrey ;

van der Flier, Wiesje M. .

LANCET, 2021, 397 (10284) :1577-1590

[6]

The amyloid-β rise and γ-secretase inhibitor potency depend on the level of substrate expression [J].

Burton, Catherine R. ;

Meredith, Jere E. ;

Barten, Donna M. ;

Goldstein, Margi E. ;

Krause, Carol M. ;

Kieras, Cathy J. ;

Sisk, Lisa ;

Iben, Lawrence G. ;

Polson, Craig ;

Thompson, Mark W. ;

Lin, Xu-Alan ;

Corsa, Jason ;

Fiedler, Tracey ;

Pierdomenico, Maria ;

Cao, Yang ;

Roach, Arthur H. ;

Cantone, Joseph L. ;

Ford, Michael J. ;

Drexler, Dieter M. ;

Olson, Richard E. ;

Yang, Michael G. ;

Bergstrom, Carl P. ;

McElhone, Kate E. ;

Bronson, Joanne J. ;

Macor, John E. ;

Blat, Yuval ;

Grafstrom, Robert H. ;

Stern, Andrew M. ;

Seiffert, Dietmar A. ;

Zaczek, Robert ;

Albright, Charles F. ;

Toyn, Jeremy H. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (34) :22992-23003

[7]

A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain [J].

De Strooper, B ;

Annaert, W ;

Cupers, P ;

Saftig, P ;

Craessaerts, K ;

Mumm, JS ;

Schroeter, EH ;

Schrijvers, V ;

Wolfe, MS ;

Ray, WJ ;

Goate, A ;

Kopan, R .

NATURE, 1999, 398 (6727) :518-522

[8]

Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice [J].

Dominguez, D ;

Tournoy, J ;

Hartmann, D ;

Huth, T ;

Cryns, K ;

Deforce, S ;

Serneels, L ;

Camacho, IE ;

Marjaux, E ;

Craessaerts, K ;

Roebroek, AJM ;

Schwake, M ;

D'Hooge, R ;

Bach, P ;

Kalinke, U ;

Moechars, D ;

Alzheimer, C ;

Reiss, K ;

Saftig, P ;

De Strooper, B .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (35) :30797-30806

[9]

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

[10]

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo [J].

Fassbender, K ;

Simons, M ;

Bergmann, C ;

Stroick, M ;

Lütjohann, D ;

Keller, P ;

Runz, H ;

Kühl, S ;

Bertsch, T ;

von Bergmannn, K ;

Hennerici, M ;

Beyreuther, K ;

Hartmann, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (10) :5856-5861

← 1 2 3 4 5 →