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Titolo:
New protease inhibitors prevent gamma-secretase-mediated production of A beta 40/42 without affecting Notch cleavage
Autore:
Petit, A; Bihel, F; da Costa, CA; Pourquie, O; Checler, F; Kraus, JL;
Indirizzi:
CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097, F-06560 Valbonne, France CNRS Valbonne France F-06560 llulaire, UMR6097, F-06560 Valbonne, France Univ Mediterranee, Fac Sci Luminy, Lab Chim Biomol, Marseille, France UnivMediterranee Marseille France , Lab Chim Biomol, Marseille, France LGPD, Unite Mixte Rech 6545, Marseille, France LGPD Marseille FranceLGPD, Unite Mixte Rech 6545, Marseille, France
Titolo Testata:
NATURE CELL BIOLOGY
fascicolo: 5, volume: 3, anno: 2001,
pagine: 507 - 511
SICI:
1465-7392(200105)3:5<507:NPIPGP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; BETA-SECRETASE; PRESENILIN-1; MATURATION; CELLS; SITE; ENDOPROTEOLYSIS; PROTEOLYSIS; ASPARTATES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Petit, A CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097, 660 Route Lucioles, F-06560 Valbonne, France CNRS 660 Route Lucioles Valbonne France F-06560 Valbonne, France
Citazione:
A. Petit et al., "New protease inhibitors prevent gamma-secretase-mediated production of A beta 40/42 without affecting Notch cleavage", NAT CELL BI, 3(5), 2001, pp. 507-511

Abstract

We have designed new non-peptidic potential inhibitors of gamma -secretaseand examined their ability to prevent production of amyloid-beta 40 (A beta 40) and A beta 42 by human cells expressing wild-type and Swedish-mutant beta -amyloid precursor protein (beta APP). Here we identify three such agents that markedly reduce recovery of both A beta 40 and A beta 42 produced by both cell lines, and increase that of C99 and C83, the carboxy-terminal fragments of beta APP that are derived from beta -and alpha -secretase, respectively, Furthermore, we show that these inhibitors do not affect endoproteolysis of endogenous or overexpressed presenilins. These inhibitors are totally unable to affect the m Delta Enotch-1 cleavage that leads to generation of the Notch intracellular domain (NICD). These represent the first non-peptidic inhibitors that are able to prevent gamma -secretase cleavage of beta APP without affecting processing of m Delta Enotch-1 or endoproteolysis of presenilins. The distinction between these two proteolytic events, which are both prevented by disruption of presenilin genes, indicates that although they are intimately linked with beta APP and Notch maturation, presenilins are probably involved in the control of maturation processes upstreamof enzymes that cleave gamma -secretase and Notch.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/02/20 alle ore 07:25:17