Artículos de revistas
Human apolipoprotein A-I binds amyloid-beta and prevents A beta-induced neurotoxicity
Fecha
2009Registro en:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v.41, n.6, p.1361-1370, 2009
1357-2725
10.1016/j.biocel.2008.12.003
Autor
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.
Institución
Resumen
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.