Conformation-specific perturbation of membrane dynamics by structurally distinct oligomers of Alzheimer's amyloid-β peptide

Abstract

The accumulation of toxic soluble oligomers of the amyloid-β peptide (Aβ) is a key step in the pathogenesis of Alzheimer’s disease. There are mainly two conformationally distinct oligomers, namely, prefibrillar...

Distinct types of amyloid‐β oligomers displaying diverse neurotoxicity mechanisms in Alzheimer's disease

“…113 Our study suggested that the A11-positive oligomers could be causing toxicity by perturbing the lipid membrane dynamics, whereas the OC-positive oligomers might bypass the toxicity by causing no change in the membrane dynamics. 113…”

“…We also found that the two conformationally distinct Aβ oligomers mature into amyloid fibrils after binding to the lipid membrane (Figure 5). 113 Our study suggested that the A11‐positive oligomers could be causing toxicity by perturbing the lipid membrane dynamics, whereas the OC‐positive oligomers might bypass the toxicity by causing no change in the membrane dynamics 113 …”

“…Our recent work investigated how the two structurally distinct, A11‐positive prefibrillar and OC‐positive fibrillar Aβ42 oligomers interact with the lipid membrane and affect the membrane integrity (Figure 5). 113 Using steady‐state fluorescence anisotropy, we showed that the A11‐positive Aβ oligomers interact with the inner hydrocarbon core of the lipid vesicles via hydrophobic C‐terminal of Aβ peptide and increase the membrane microviscosity of lipid vesicles derived from brain total lipid extract. Our picoseconds time‐resolved fluorescence anisotropy data showed that the N‐terminal of A11‐positive Aβ oligomers undergo a membrane‐induced conformational change, allowing the oligomers to insert deep into the lipid bilayer and perturb the membrane dynamics.…”

“…Mechanism of the interaction of structurally distinct Aβ42 oligomers with the large unilamellar vesicles of brain total lipid extract. Adapted from Madhu et al 113 (Copyright Royal Society of Chemistry) localized in various compartments of the cell. Other than the generation of Aβ intracellular, the extracellular Aβ can be internalized through numerous receptors.…”

“…Mechanism of the interaction of structurally distinct Aβ42 oligomers with the large unilamellar vesicles of brain total lipid extract. Adapted from Madhu et al 113 (Copyright Royal Society of Chemistry)…”