Human apolipoprotein A-I binds amyloid-beta and prevents A beta-induced neurotoxicity

Paula-Lima, Andrea C.; Tricerri, M. Alejandra; Brito-Moreira, Jordano; Bomfim, Theresa R.; Oliveira, Fabio F.; Magdesian, Margaret H.; Grinberg, Lea T.; Panizzutti, Rogerio; Ferreira, Sergio T.

Abstract

Aggregates of the amyloid-P peptide (A beta) play a central role in the pathogenesis of Alzheimer's disease (AD). Identification of proteins that physiologically bind A beta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated A beta(1-42), We isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and A beta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by A beta. Significantly, A beta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from A beta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates A beta aggregation and A beta-induced neuronal damage and that the A beta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of A beta toxicity. (C) 2009 Published by Elsevier Ltd.

Más información

Título según WOS: ID WOS:000264669300019 Not found in local WOS DB
Título de la Revista: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volumen: 41
Número: 6
Editorial: PERGAMON-ELSEVIER SCIENCE LTD
Fecha de publicación: 2009
Página de inicio: 1361
Página final: 1370
DOI:

10.1016/j.biocel.2008.12.003

Notas: ISI