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Titolo:
Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits A beta aggregation and toxicity
Autore:
Koldamova, RP; Lefterov, IM; Lefterova, MI; Lazo, JS;
Indirizzi:
Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 armacol, Pittsburgh, PA 15261 USA
Titolo Testata:
BIOCHEMISTRY
fascicolo: 12, volume: 40, anno: 2001,
pagine: 3553 - 3560
SICI:
0006-2960(20010327)40:12<3553:AADIWA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN BLEOMYCIN HYDROLASE; HUMAN CEREBROSPINAL-FLUID; ALPHA-SECRETASE CLEAVAGE; HIGH-DENSITY-LIPOPROTEIN; ALZHEIMERS-DISEASE; LATE-ONSET; FIBRIL FORMATION; APO-E; BRAIN; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Lazo, JS Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 Pittsburgh, PA 15261 USA
Citazione:
R.P. Koldamova et al., "Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits A beta aggregation and toxicity", BIOCHEM, 40(12), 2001, pp. 3553-3560

Abstract

Amyloid precursor protein (APP) is the source of the neurotoxic amyloid beta (A beta) peptide associated with Alzheimer's disease. Apolipoprotein A-I(apoA-I), a constituent of high-density lipoprotein complexes, was identified by a yeast two-hybrid system as a strong and specific binding partner of full-length APP (APPfl). This association between apoA-I and APPfl was localized to the extracellular domain of APP (APPextra). Furthermore, the interaction between apoA-I and APPfl was confirmed by coprecipitation using recombinant epitope-tagged APPextra and purified apoA-I. Several functional domains have been identified in APPextra, and we focused on a possible interaction between apoA-1 and the pathologically important AP peptide, because APPextra contains the nontransmembrane domain of A beta. The binding between apoA-I and A beta was saturable (K-d = 6 nM), specific, and reversible. APPextra also competed with apoA-I for binding to A beta. Direct evidence for this interaction was obtained by the formation of an SDS-resistant A beta-apoA-I complex in polyacrylamide gels. Competitive experiments with apolipoprotein E (isoforms E2 and E4) showed that apoA-I had a higher binding affinity for A beta. We also found that apoA-I inhibited the beta -sheet formation of A beta with a mean inhibitory concentration close to that of alpha2-macroglobulin. Finally, we demonstrated that apoA-I attenuated A beta -induced cytotoxicity. These results suggest apoA-I binds to at least one extracellular domain of APP and has a functional role in controlling A beta aggregation and toxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 05:10:30