title: Amyloidogenicity and toxicity of the reverse and scrambled variants of amyloid-β 1-42.
abstract: β-amyloid 1-42 (Aβ1-42) is a self-assembling peptide that goes through many conformational and morphological changes before forming the fibrils that are deposited in extracellular plaques characteristic of Alzheimer's disease. The link between Aβ1-42 structure and toxicity is of major interest, in particular, the neurotoxic potential of oligomeric species. Many studies utilise reversed (Aβ42-1) and scrambled (AβS) forms of amyloid-β as control peptides. Here, using circular dichroism, thioflavin T fluorescence and transmission electron microscopy, we reveal that both control peptides self-assemble to form fibres within 24 h. However, oligomeric Aβ reduces cell survival of hippocampal neurons, while Aβ42-1 and Aβs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils.
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, UK.
authors.forename: Devkee M
authors.initials: DM
authors.lastname: Vadukul
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, UK.
authors.forename: Oyinkansola
authors.initials: O
authors.lastname: Gbajumo
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Marshall
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, UK.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000633:toxicity*; D058227:Amyloidogenic Proteins / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D052160:Benzothiazoles; D002470:Cell Survival / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000633:toxicity*; D061251:Primary Cell Culture; D000072757:Protein Conformation, beta-Strand; D051381:Rats; D013050:Spectrometry, Fluorescence; D013844:Thiazoles
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058227:Amyloidogenic Proteins; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T
keywords: Alzheimer's disease; amyloid fibril; amyloid-β, control; cytotoxicity; self-assembly