Specific binding of DNA to aggregated forms of Alzheimer's disease amyloid peptides.
Anomalous protein aggregation is closely associated to age-related mental illness. Extraneuronal plaques, mainly composed of aggregated amyloid peptides, are considered as hallmarks of Alzheimer's disease. According to the amyloid cascade hypothesis, this disease starts as a consequence of an abnormal processing of the amyloid precursor protein resulting in an excess of amyloid peptides. Nuclear localization of amyloid peptide aggregates together with amyloid-DNA interaction, have been repeatedly reported. In this paper we have used surface plasmon resonance and electron microscopy to study the structure and behavior of different peptides and proteins, including β-lactoglobulin, bovine serum albumin, myoglobin, histone, casein and the amyloid-β peptides related to Alzheimer's disease Aβ25-35 and Aβ1-40. The main purpose of this study is to investigate whether proneness to DNA interaction is a general property displayed by aggregated forms of proteins, or it is an interaction specifically related to the aggregated forms of those particular proteins and peptides related to neurodegenerative diseases. Our results reveal that those aggregates formed by amyloid peptides show a particular proneness to interact with DNA. They are the only aggregated structures capable of binding DNA, and show more affinity for DNA than for other polyanions like heparin and polyglutamic acid, therefore strengthening the hypothesis that amyloid peptides may, by means of interaction with nuclear DNA, contribute to the onset of Alzheimer's disease.
Departamento de Química Física Aplicada, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Sergio
S
Camero
Jose M
JM
Ayuso
Alejandro
A
Barrantes
María J
MJ
Benítez
Juan S
JS
Jiménez
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D011485:Protein Binding; D012996:Solutions / Q000737:chemistry; D020349:Surface Plasmon Resonance
D016229:Amyloid beta-Peptides; D006657:Histones; D012996:Solutions; D004247:DNA