Title
Amyloidogenicity and toxicity of the reverse and scrambled variants of Amyloid-β 1-42
Author
Devkee M. Vadukul, Oyinkansola Gbajumo, Karen E. Marshall, Louise C. Serpell
Year
2017
Journal
FEBS Letters
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 fibres within 24 hours. However, oligomeric Aβ reduces cell survival of hippocampal neurons, whilst Aβ42-1 and Aβs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Aggregation, Biochemistry