title: Effect of the Interaction of the amyloid β (1-42) peptide with short single-stranded synthetic nucleotide sequences: morphological characterization of the inhibition of fibrils formation and fibrils disassembly.
abstract: The formation of extracellular neuritic plaques in the brain of individuals who suffered from Alzheimer's disease (AD) is a major pathological hallmark. These plaques consist of filamentous aggregates of the amyloid beta (1-42) (Aβ42) proteins. Prevention or reduction of the formation of these fibrils is foreseen as a potential therapeutic approach. In this context, we investigated the interactions between the Aβ42 protein and polyions, in particular short single stranded synthetic nucleotide sequences. The experimental outcomes reported herein provide evidence of the inhibition of amyloid fibril genesis as well as disassembly of existing fibers through electrostatic interaction between the Aβ42 protein and the polyions. Since the polyions and the Aβ42 protein are oppositely charged, the formation of (micellar) inter polyelectrolyte complexes (IPECs) is likely to occur. Since the abnormal deposition of amyloid fibers is an archetype of AD, the outcomes of these investigations, supported by atomic force microscopy imaging in the dry and liquid states, as well as circular dichroism and Fourier transform infrared spectroscopy, are of high interest for the development of future strategies to cure a disease that concerns an ever aging population.
authors.affiliation: Faculty of Sciences, Department of Inorganic and Analytical Chemistry, University of Geneva , Quai Ernest Ansermet 30, CH-1211, Geneva 4, Switzerland.
authors.forename: Jancy Nixon
authors.initials: JN
authors.lastname: Abraham
authors.forename: Dawid
authors.initials: D
authors.lastname: Kedracki
authors.forename: Enora
authors.initials: E
authors.lastname: Prado
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gourmel
authors.forename: Plinio
authors.initials: P
authors.lastname: Maroni
authors.forename: Corinne
authors.initials: C
authors.lastname: Nardin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D066263:Protein Aggregation, Pathological; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D016229:Amyloid beta-Peptides; D009841:Oligonucleotides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)