Interaction between Alzheimer's Abeta1-42 peptide and DNA detected by surface plasmon resonance.
Alzheimer's disease is a form of senile mental disorder characterized by the presence of extracellular plaques, containing amyloid-beta (Abeta) as the main component. According to the amyloid hypothesis, an increase of extracellular Abeta production is in the origin of the aberrant plaques causing neuronal loss and dementia. However, a wealth of evidence has been accumulated pointing to the toxicity of soluble intracellular Abeta, having different morphologies of aggregation, as the origin of the neurodegenerative process. The exact nature of the initial molecular events by which Abeta exerts its neurotoxicity, remains obscure. Different forms of soluble Abeta peptide aggregates have been recently found to reside in the nucleus of CHO cells and Alzheimer's disease brain samples. This paper focus mainly on the interaction between DNA and the 42 residue Abeta (Abeta42) as studied by Surface Plasmon Resonance. Electronic microscopy and UV-visible spectroscopy are also used to further characterize the interaction. Particular attention is paid to the extent of Abeta42 aggregation needed to observe the interaction with DNA. Our results show that DNA binds all soluble aggregate forms of Abeta42, therefore suggesting that DNA binding is a general property of different soluble forms of Abeta42, unrelated to the extent of aggregation.
Barrantes
Alejandro
A
Centro de Biología Molecular Severo Ochoa. Cantoblanco, 28049 Madrid, Spain.
Rejas
María T
MT
Benítez
María J
MJ
Jiménez
Juan S
JS
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000648:ultrastructure; D002449:Cell Aggregation; D004247:DNA / Q000032:analysis*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D004247:DNA