INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
artículos
Título:
Human apolipoprotein A-I binds amyloid-ß and prevents Aß-induced neurotoxicity
Autor/es:
PAULA-LIMA, A. C.; TRICERRI, M. A.; BRITO-MOREIRA, J.; BOMFIM, T. R.; OLIVEIRA, F. F.; MAGDESIAN, M. H.; GRINGBERG, L. T.; PANIZZUTTI, R.; FERREIRA, S. T.
Revista:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY
Editorial:
Elsevier
Referencias:
Lugar: Netherlands; Año: 2009 vol. 41 p. 1361 - 1370
ISSN:
1357-2725
Resumen:
Aggregates of the amyloid-beta peptide (Abeta) play a central role in the pathogenesis of Alzheimer´s disease (AD). Identification of proteins that physiologically bind Abeta 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 Abeta(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 Abeta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by Abeta. Significantly, Abeta/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 Abeta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates Abeta aggregation and Abeta-induced neuronal damage and that the Abeta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of Abeta toxicity