Affiliations: [a] Departamento de Química Física Aplicada, Universidad Autónoma de Madrid, Spain | [b] Centro de Biología Molecular Severo Ochoa. Cantoblanco, 28049 Madrid, Spain
Abstract: Alzheimer's disease is a form of senile mental disorder characterized by the presence of extracellular plaques, containing amyloid-β (Aβ) as the main component. According to the amyloid hypothesis, an increase of extracellular Aβ 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 Aβ, having different morphologies of aggregation, as the origin of the neurodegenerative process. The exact nature of the initial molecular events by which Aβ exerts its neurotoxicity, remains obscure. Different forms of soluble Aβ 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 Aβ (Aβ42) 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 Aβ42 aggregation needed to observe the interaction with DNA. Our results show that DNA binds all soluble aggregate forms of Aβ42, therefore suggesting that DNA binding is a general property of different soluble forms of Aβ42, unrelated to the extent of aggregation.
Keywords: Protein aggregation and interaction, neurotoxicity, mental disease
