Biomedicine - A portrait of Alzheimer secretases - New features and familiar faces

被引：443

作者：

Esler, WP

Wolfe, MS ^{[1
]}

机构：

[1] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

SCIENCE | 2001年 / 293卷 / 5534期

关键词：

D O I：

10.1126/science.1064638

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The amyloid beta -peptide (A beta) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40- to 42-amino acid peptide is formed by the cleavage of the A beta precursor protein (APP). The three proteases that cleave APP, alpha-, beta-, and gamma -secretases, have been implicated in the etiology of AD. beta -Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and alpha -secretase displays characteristics of certain membrane-tethered metalloproteases. gamma -Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the alpha-, beta-, and gamma -secretases provides potential targets for designing new drugs to treat AD.

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收藏

页码：1449 / 1454

页数：6

相关论文

共 108 条

[21] Mice lacking both presenilin genes exhibit early embryonic patterning defects [J].

Donoviel, DB ;

Hadjantonakis, AK ;

Ikeda, M ;

Zheng, H ;

Hyslop, PS ;

Bernstein, A .

GENES & DEVELOPMENT, 1999, 13 (21) :2801-2810

[22] Increased amyloid-beta 42(43) in brains of mice expressing mutant presenilin 1 [J].

Duff, K ;

Eckman, C ;

Zehr, C ;

Yu, X ;

Prada, CM ;

Pereztur, J ;

Hutton, M ;

Buee, L ;

Harigaya, Y ;

Yager, D ;

Morgan, D ;

Gordon, MN ;

Holcomb, L ;

Refolo, L ;

Zenk, B ;

Hardy, J ;

Younkin, S .

NATURE, 1996, 383 (6602) :710-713

[23] Second-site cleavage in sterol regulatory element-binding protein occurs at transmembrane junction as determined by cysteine panning [J].

Duncan, EA ;

Davé, UP ;

Sakai, J ;

Goldstein, JL ;

Brown, MS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (28) :17801-17809

[24] CLEAVAGE OF AMYLOID-BETA PEPTIDE DURING CONSTITUTIVE PROCESSING OF ITS PRECURSOR [J].

ESCH, FS ;

KEIM, PS ;

BEATTIE, EC ;

BLACHER, RW ;

CULWELL, AR ;

OLTERSDORF, T ;

MCCLURE, D ;

WARD, PJ .

SCIENCE, 1990, 248 (4959) :1122-1124

[25] Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1 [J].

Esler, WP ;

Kimberly, WT ;

Ostaszewski, BL ;

Diehl, TS ;

Moore, CL ;

Tsai, JY ;

Rahmati, T ;

Xia, WM ;

Selkoe, DJ ;

Wolfe, MS .

NATURE CELL BIOLOGY, 2000, 2 (07) :428-434

[26] BACE2, a β-secretase homolog, cleaves at the β site and within the amyloid-β region of the amyloid-β precursor protein [J].

Farzan, M ;

Schnitzler, CE ;

Vasilieva, N ;

Leung, D ;

Choe, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (17) :9712-9717

[27] REVERSAL OF THE SWEDISH FAMILIAL ALZHEIMERS-DISEASE MUTANT PHENOTYPE IN CULTURED-CELLS TREATED WITH PHORBOL 12,13-DIBUTYRATE [J].

FELSENSTEIN, KM ;

INGALLS, KM ;

HUNIHAN, LW ;

ROBERTS, SB .

NEUROSCIENCE LETTERS, 1994, 174 (02) :173-176

[28] Design of potent inhibitors for human brain memapsin 2 (β-secretase) [J].

Ghosh, AK ;

Shin, DW ;

Downs, D ;

Koelsch, G ;

Lin, XL ;

Ermolieff, J ;

Tang, J .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (14) :3522-3523

[29] SEGREGATION OF A MISSENSE MUTATION IN THE AMYLOID PRECURSOR PROTEIN GENE WITH FAMILIAL ALZHEIMERS-DISEASE [J].

GOATE, A ;

CHARTIERHARLIN, MC ;

MULLAN, M ;

BROWN, J ;

CRAWFORD, F ;

FIDANI, L ;

GIUFFRA, L ;

HAYNES, A ;

IRVING, N ;

JAMES, L ;

MANT, R ;

NEWTON, P ;

ROOKE, K ;

ROQUES, P ;

TALBOT, C ;

PERICAKVANCE, M ;

ROSES, A ;

WILLIAMSON, R ;

ROSSOR, M ;

OWEN, M ;

HARDY, J .

NATURE, 1991, 349 (6311) :704-706

[30] AMYLOID BETA-PEPTIDE IS PRODUCED BY CULTURED-CELLS DURING NORMAL METABOLISM [J].

HAASS, C ;

SCHLOSSMACHER, MG ;

HUNG, AY ;

VIGOPELFREY, C ;

MELLON, A ;

OSTASZEWSKI, BL ;

LIEBERBURG, I ;

KOO, EH ;

SCHENK, D ;

TEPLOW, DB ;

SELKOE, DJ .

NATURE, 1992, 359 (6393) :322-325

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