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Titolo:
Intracellular apolipoprotein E affects amyloid precursor protein processing and amyloid A beta production in COS-1 cells
Autore:
Hass, S; Weidemann, A; Utermann, G; Baier, G;
Indirizzi:
Innsbruck Univ, Inst Med Biol & Human Genet, A-6020 Innsbruck, Austria Innsbruck Univ Innsbruck Austria A-6020 Genet, A-6020 Innsbruck, Austria Univ Heidelberg, Ctr Biol Mol, D-69120 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69120 , D-69120 Heidelberg, Germany
Titolo Testata:
MOLECULAR GENETICS AND GENOMICS
fascicolo: 5, volume: 265, anno: 2001,
pagine: 791 - 800
SICI:
1617-4615(200107)265:5<791:IAEAAP>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPORADIC ALZHEIMERS-DISEASE; IN-VITRO; PEPTIDE DEPOSITION; SECRETORY PATHWAY; TRANSGENIC MICE; TYPE-4 ALLELE; MESSENGER-RNA; BREFELDIN-A; E ISOFORMS; EXPRESSION;
Keywords:
Alzheimer's disease; apoE alleles; ApoE targeting mutants; endoplasmic reticulum, amyloid precursor protein (APP) processing;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Baier, G Innsbruck Univ, Inst Med Biol & Human Genet, Schoepfstr 41, A-6020 Innsbruck, Austria Innsbruck Univ Schoepfstr 41 Innsbruck Austria A-6020k, Austria
Citazione:
S. Hass et al., "Intracellular apolipoprotein E affects amyloid precursor protein processing and amyloid A beta production in COS-1 cells", MOL GENET G, 265(5), 2001, pp. 791-800

Abstract

The apoE gene has been identified as a major susceptibility locus for late-onset, Alzheimer's disease (LOAD). The epsilon4 allele greatly reduces ageof onset of LOAD as compared to the wild-type epsilon3 allele. The molecular mechanism(s) underlying the association has not yet been fully elucidated. The apoE protein has been shown to physically interact with the A beta region of the Amyloid Precursor Protein (APP), but also with the ectodomain of the APP holoprotein itself. In this study we have used apoE fusion proteins containing either the ER retention sequence KDEL or trans-Golgi network(TGN) signal sequence in order to define potential apoE-mediated alterations in APP protein processing. Co-expression and pulse-chase experiments showed that a functional apoE:APP interaction occurs intracellularly which directly affects maturation and subsequently the secretion kinetics of A-PP. In addition, an epsilon4 allele-specific induction of A beta production has been demonstrated. apoE3 resulted in increased A beta production only when targeted to the ER, as observed in cells transfected with an apoE3KDEL fusion protein as well as following treatment with brefeldin A. The findings suggest that in cells that express both apoE and APP, such as astrocytes and microglia, a functional apoE:APP interaction may occur which modulates APP processing and A beta production.

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Documento generato il 25/01/20 alle ore 03:15:51