Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ALZHEIMERS-DISEASE-LINKED MUTATION OF PRESENILIN-2 (N1411-PS2) DRASTICALLY LOWERS APP-ALPHA SECRETION - CONTROL BY THE PROTEASOME
Autore:
MARAMBAUD P; DACOSTA CA; ANCOLIO K; CHECLER F;
Indirizzi:
INST PHARMACOL MOL & CELLULAIRE,CNRS,UPR 411,660 ROUTE LUCIOLES F-06560 VALBONNE FRANCE INST PHARMACOL MOL & CELLULAIRE,CNRS,UPR 411 F-06560 VALBONNE FRANCE
Titolo Testata:
Biochemical and biophysical research communications (Print)
fascicolo: 1, volume: 252, anno: 1998,
pagine: 134 - 138
SICI:
0006-291X(1998)252:1<134:AMOP(D>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; BETA-PROTEIN; DERIVATIVES; CLEAVAGE; GENETICS; GENES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
P. Marambaud et al., "ALZHEIMERS-DISEASE-LINKED MUTATION OF PRESENILIN-2 (N1411-PS2) DRASTICALLY LOWERS APP-ALPHA SECRETION - CONTROL BY THE PROTEASOME", Biochemical and biophysical research communications (Print), 252(1), 1998, pp. 134-138

Abstract

Most of early onset familial forms of Alzheimer's disease (FAD) are due to inherited mutations located on two homologous proteins, presenilins 1 and 2 (PS1 and PS2) encoded by chromosomes 14 and 1, respectively. Here we show that the expression of wild type (wt)-PS2 in human HEK293 cells increases the production of the physiological alpha-secretase-derived product, APP alpha. By contrast, APP alpha secretion is drastically reduced in cells expressing the FAD-linked N141I-PS2. We establish that wt-PS2, N141I-PS2 and their C-terminal maturation fragment are degraded by the enzymatic multicatalytic complex, proteasome. Interestingly, two selective proteasome inhibitors, Z-IE(Ot-Bu)A-Leucinal and lactacystin potentiate the APP alpha secretion observed in wtPS2-expressing cells and further amplify the N141I-PS2-induced decrease in APP alpha production. By contrast, a series of pharmacological agents unable to affect the proteasome do not modify PS2 immunoreactivities and APP alpha recoveries. Altogether, our data indicate that: 1) wtPS2 positively modulates the alpha-secretase physiological pathway of beta APP maturation in human cells; 2) N141I mutation on PS2 drastically lowers the secretion of APP alpha; 3) Proteasome inhibitors prevent the degradation of wtPS2, N141I-PS2 and their C-terminal maturation product. This protection against proteasomal degradation directly modulates the APP alpha secretion response elicited by wt- and FAD-linked PS2 expression in human HEK293 cells. (C) 1998 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 16:55:34