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Titolo:
Role of apolipoprotein E receptors in regulating the differential in vivo neurotrophic effects of apolipoprotein E
Autore:
Veinbergs, I; Van Uden, E; Mallory, M; Alford, M; McGiffert, C; DeTeresa, R; Orlando, R; Masliah, E;
Indirizzi:
Univ Calif San Diego, Dept Neurosci, Sch Med, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 ch Med, La Jolla, CA 92093 USA Univ Calif San Diego, Dept Pathol, Sch Med, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 ch Med, La Jolla, CA 92093 USA
Titolo Testata:
EXPERIMENTAL NEUROLOGY
fascicolo: 1, volume: 170, anno: 2001,
pagine: 15 - 26
SICI:
0014-4886(200107)170:1<15:ROAERI>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
DENSITY-LIPOPROTEIN RECEPTOR; CENTRAL-NERVOUS-SYSTEM; E-DEFICIENT MICE; AMYLOID PRECURSOR PROTEIN; E MESSENGER-RNA; ALZHEIMERS-DISEASE; TRANSGENIC MICE; NEURITE OUTGROWTH; KNOCKOUT MICE; IN-VIVO;
Keywords:
apoE; LDL-R; LRP; MAP2; RAP; somatostatin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Masliah, E Univ Calif San Diego, Dept Neurosci, Sch Med, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 Jolla, CA 92093 USA
Citazione:
I. Veinbergs et al., "Role of apolipoprotein E receptors in regulating the differential in vivo neurotrophic effects of apolipoprotein E", EXP NEUROL, 170(1), 2001, pp. 15-26

Abstract

Apolipoprotein E (apoE) is known to bind to at least five receptors, including the low-density lipoprotein (LDL) receptor-related protein (LRP), verylow density LDL receptor (VLDL-R), LDL-R, apoE receptor 2 (apoER2), and megalin/gp330. In this context, the main objective of the present study was to better understand the contributions of LRP and LDL-R to the in vivo neurotrophic effects of apoE. For this purpose, apoE-deficient and receptor-associated protein (RAP)deficient mice were infused with recombinant apoE3, RAP, or saline. Infusion of apoE3 into apoE-deficient mice resulted in amelioration of degenerative alterations of pyramidal neurons, but had no effect on somatostatin-producing interneurons. In contrast, infusion of apoE3 into RAP-deficient mice resulted in amelioration of degenerative alterations of somatostatin-producing interneurons. LRP and LDL-R levels were significantly reduced in RAP-deficient mice, but significantly increased in the apoE-deficient mice. In contrast, levels of apoE were reduced in the RAP-eficient mice compared to wildtype controls, suggesting that neurotrophic effects ofapoE3 in the RAP-deficient mice were related to a combined deficit in endogenous apoE and selected apoE receptors. Furthermore, in apoE-deficient mice, infusion of apoE3 had a neurotrophic effect on somatostatin-producing interneurons only when combined with RAP, suggesting that increased expression of apoE receptors in apoE-deficient mice prevented apoE from rescuing somatostatin-producing neurons. This study supports the contention that some of the in vivo neurotrophic effects of apoE are mediated by LRP and LDL-R and that a critical balance between levels of apoE and its receptors is necessary for the differential neurotrophic effects to appear. (C) 2001 AcademicPress.

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Documento generato il 25/11/20 alle ore 01:03:50