Alzheimer%26apos;s Disease Amyloid Peptides Interact with DNA, As Proved by Surface Plasmon Resonance

作者：Barrantes Alejandro; Camero Sergio; Garcia Lucas Angel; Navarro Pedro J; Benitez Maria J; Jimenez Juan S^*

来源：Current Alzheimer Research, 2012, 9(8): 924-934.

DOI：10.2174/156720512803251101

• Alzheimer
• amyloid
• DNA
• surface plasmon resonance

According to the amyloid hypothesis, abnormal processing of the beta-amyloid precursor protein in Alzheimer%26apos;s disease patients increases the production of beta-amyloid toxic peptides, which, after forming highly aggregated fibrillar structures, lead to extracellular plaques formation, neuronal loss and dementia. However, a great deal of evidence has point to intracellular small oligomers of amyloid peptides, probably transient intermediates in the process of fibrillar structures formation, as the most toxic species. In order to study the amyloid-DNA interaction, we have selected here three different forms of the amyloid peptide: A beta 1-40, A beta 25-35 and a scrambled form of A beta 25-35. Surface Plasmon Resonance was used together with UV-visible spectroscopy, Electrophoresis and Electronic Microscopy to carry out this study. Our results prove that, similarly to the full length A beta 1-42, all conformations of toxic amyloid peptides, A beta 1-40 and A beta 25-35, may bind DNA. In contrast, the scrambled form of A beta 25-35, a non-aggregating and nontoxic form of this peptide, could not bind DNA. We conclude that although the amyloid-DNA interaction is closely related to the amyloid aggregation proneness, this cannot be the only factor which determines the interaction, since small oligomers of amyloid peptides may also bind DNA if their predominant negatively charged amino acid residues are previously neutralized.

• 出版日期2012-10