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Titolo:
Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts
Autore:
Riddell, DR; Christie, G; Hussain, I; Dingwall, C;
Indirizzi:
GlaxoSmithKline, Neurol Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England GlaxoSmithKline Harlow Essex England CM19 5AW ow CM19 5AW, Essex, England
Titolo Testata:
CURRENT BIOLOGY
fascicolo: 16, volume: 11, anno: 2001,
pagine: 1288 - 1293
SICI:
0960-9822(20010821)11:16<1288:COB(IL>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; INSOLUBLE MEMBRANE COMPARTMENT; ALZHEIMERS-DISEASE; TRANSFECTED CELLS; PLASMA-MEMBRANE; CHOLESTEROL; COMPLEXES; DOMAINS; ALLELE; RISK;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Dingwall, C GlaxoSmithKline, Neurol Ctr Excellence Drug Discovery, New Frontiers Sci Pk,3rd Ave, Harlow CM19 5AW, Essex, England GlaxoSmithKline New Frontiers Sci Pk,3rd Ave Harlow Essex England CM19 5AW
Citazione:
D.R. Riddell et al., "Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts", CURR BIOL, 11(16), 2001, pp. 1288-1293

Abstract

Recent epidemiological studies show a reduced prevalence of Alzheimer's disease (AD) in patients treated with inhibitors of cholesterol biosynthesis [1, 2]. Moreover, the cholesterol-transport protein, apolipoprotein E4, andelevated cholesterol are important risk factors for AD [3-5]. Additionally, in vitro and in vivo studies show that intracellular cholesterol levels can modulate the processing of amyloid precursor protein (APP) to beta -amyloid [6-11], the major constituent of senile plaques [12-14]. Cholesterol plays a crucial role in maintaining lipid rafts in a functional state [15]. Lipid rafts are cholesterol-enriched membrane microdomains implicated in signal transduction, protein trafficking, and proteolytic processing [15-18]. Since APP, beta -amyloid, and the putative gamma -secretase, presenilin-1 (PS-1), have all been found in lipid rafts [12, 19-21], we hypothesized thatthe recently identified beta -secretase, Asp2 (BACE1) [13], might also be present in rafts. Here, we report that recombinant Asp2 expressed in three distinct cell lines is raft associated. Using both detergent and nondetergent methods, Asp2 protein and activity were found in a light membrane raft fraction that also contained other components of the amyloidogenic pathway. Immunoisolation of caveolin-containing vesicles indicated that Asp2 was present in a unique raft population distinct from caveolae. Finally, depletionof raft cholesterol abrogated association of Asp2 with the light membrane fraction. These observations are consistent with the raft localization of APP processing and suggest that the partitioning of Asp2 into lipid rafts may underlie the cholesterol sensitivity of beta -amyloid production.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 13:03:39