Gamma-secretase as a pharmacological target in Alzheimer disease research: When, why and how?

被引：14

作者：

Ziani-Cherif, Chewki ^{[1
]}

Mostefa-Kara, Bachir ^{[1
]}

Brixi-Gormat, Fatima Z. ^{[1
]}

机构：

[1] Univ Abou Bekr Balkaid, Lab Catalyse & Chim Fine, Tilimsen 13000, Algeria

来源：

CURRENT PHARMACEUTICAL DESIGN | 2006年 / 12卷 / 33期

关键词：

Alzheimer disease; amyloid beta precursor protein; amyloid beta; gamma-secretase; presenilins; gamma-secretase inhibitors; non-steroidal anti-inflammatory drugs;

D O I：

10.2174/138161206778792994

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the form of senile plaques as well as neurofibrillary tangles (NFTs) in the brain. In the amyloidogenic pathway, the amyloid-beta precursor protein (APP) is cleaved by beta-secretase first, followed by gamma-secretase cleavage producing therefore A beta. This review summarizes the recent findings in the AD field and focuses on the different gamma-secretase inhibitors that have been developed as a therapeutic approach toward AD.

引用

页码：4313 / 4335

页数：23

共 230 条

[81]

Harrison T, 2004, CURR OPIN DRUG DISC, V7, P709

[82]

Heber S, 2000, J NEUROSCI, V20, P7951

[83] Quantitative MRI assessment of Alzheimer's disease [J].

Helpern, JA ;

Jensen, J ;

Lee, SP ;

Falangola, MF .

JOURNAL OF MOLECULAR NEUROSCIENCE, 2004, 24 (01) :45-48

[84] Total inactivation of γ-secretase activity in presenilin-deficient embryonic stem cells [J].

Herreman, A ;

Serneels, L ;

Annaert, W ;

Collen, D ;

Schoonjans, L ;

De Strooper, B .

NATURE CELL BIOLOGY, 2000, 2 (07) :461-462

[85] Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency [J].

Herreman, A ;

Hartmann, D ;

Annaert, W ;

Saftig, P ;

Craessaerts, K ;

Serneels, L ;

Umans, L ;

Schrijvers, V ;

Checler, F ;

Vanderstichele, H ;

Baekelandt, V ;

Dressel, R ;

Cupers, P ;

Huylebroeck, D ;

Zwijsen, A ;

Van Leuven, F ;

De Strooper, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) :11872-11877

[86] INHIBITION OF BETA-AMYLOID FORMATION IDENTIFIES PROTEOLYTIC PRECURSORS AND SUBCELLULAR SITE OF CATABOLISM [J].

HIGAKI, J ;

QUON, D ;

ZHONG, ZY ;

CORDELL, B .

NEURON, 1995, 14 (03) :651-659

[87] A combinatorial approach to the identification of dipeptide aldehyde inhibitors of β-amyloid production [J].

Higaki, JN ;

Chakravarty, S ;

Bryant, CM ;

Cowart, LR ;

Harden, P ;

Scardina, JM ;

Mavunkel, B ;

Luedtke, GR ;

Cordell, B .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (19) :3889-3898

[88] 19F and 1H MRI detection of amyloid β plaques in vivo [J].

Higuchi, M ;

Iwata, N ;

Matsuba, Y ;

Sato, K ;

Sasamoto, K ;

Saido, TC .

NATURE NEUROSCIENCE, 2005, 8 (04) :527-533

[89] Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17 [J].

Hong, M ;

Zhukareva, V ;

Vogelsberg-Ragaglia, V ;

Wszolek, Z ;

Reed, L ;

Miller, BI ;

Geschwind, DH ;

Bird, TD ;

McKeel, D ;

Goate, A ;

Morris, JC ;

Wilhelmsen, KC ;

Schellenberg, GD ;

Trojanowski, JQ ;

Lee, VMY .

SCIENCE, 1998, 282 (5395) :1914-1917

[90] Nicastrin is required for γ-secretase cleavage of the Drosophila Notch receptor [J].

Hu, Y ;

Ye, YH ;

Fortini, ME .

DEVELOPMENTAL CELL, 2002, 2 (01) :69-78

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