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Titolo:
Astrocytes down-regulate neuronal beta-amyloid precursor protein expression and modify its processing in an apolipoprotein E isoform-specific manner
Autore:
Vincent, B; Smith, JD;
Indirizzi:
Inst Pharmacol Mol & Cellulaire, CNRS, UMR 6097, F-06560 Valbonne, France Inst Pharmacol Mol & Cellulaire Valbonne France F-06560 Valbonne, France Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10021 USA Rockefeller Univ New York NY USA 10021 Metab Lab, New York, NY 10021 USA
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 2, volume: 14, anno: 2001,
pagine: 256 - 266
SICI:
0953-816X(200107)14:2<256:ADNBPP>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BINDING ACTIVITY; ALZHEIMERS-DISEASE BRAIN; CENTRAL-NERVOUS-SYSTEM; TRANSGENIC MICE; IN-VITRO; PEPTIDE DEPOSITION; CEREBRAL-CORTEX; TYPE-4 ALLELE; E GENOTYPE; CULTURES;
Keywords:
Alzheimer; apolipoprotein E; astrocytes; neurons; transgenic mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Vincent, B Inst Pharmacol Mol & Cellulaire, CNRS, UMR 6097, 660 Route Lucioles, F-06560 Valbonne, France Inst Pharmacol Mol & Cellulaire 660 Route Lucioles Valbonne France F-06560
Citazione:
B. Vincent e J.D. Smith, "Astrocytes down-regulate neuronal beta-amyloid precursor protein expression and modify its processing in an apolipoprotein E isoform-specific manner", EUR J NEURO, 14(2), 2001, pp. 256-266

Abstract

Alzheimer's disease is the most frequent neurodegenerative disorder in theaged population and is characterized by the deposition of the 40/42-residue amyloid beta protein (A beta), a proteolytic fragment of the beta -amyloid precursor protein (APP). A common apolipoprotein E (apoE) polymorphism isassociated with an increased risk of developing the disease. In order to assess the putative relationship between apoE and amyloidogenesis in the CNS, we prepared primary cortical neurons overexpressing humanized APP(695) bearing the Swedish mutation (hAPP(695SW)) and we analysed APP expression andprocessing after: (i) coculture with primary astrocytes from wild-type, apoE-deficient (EO) mice, or mice overexpressing human apoE2, E3, or E4; (ii)treatment with conditioned media from apoE0, E2, E3 or E4 astrocytes; and (iii) treatment with human recombinant ApoE or human apoE purified from conditioned media of stably transfected RAW264 cells (E2, E3 and E4). Interestingly, a strong decrease in APP expression was observed only when neurons were cocultured with astrocytes (and independently of the apoE genotype considered), suggesting that cell-cell contact is required. Moreover, apoE4-secreting astrocytes, but not recombinant or purified apoE4, significantly increased A beta production and decrease sAPP alpha secretion only when cultured in direct contact with neurons, whereas apoE2 astrocytes had a protective effect. We conclude that astrocytes: (i) strongly regulate neuronal APP expression in primary neurons, and (ii) promote the amyloidogenic pathway inan apoE4-dependent manner. Thus, apoE and astrocytic factor(s) may modulate the pathogenesis of Alzheimer's disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/01/20 alle ore 16:06:16