Aβ under stress: the effects of acidosis, Cu2+-binding, and oxidation on amyloid β-peptide dimers. Issue 56 (27th June 2018)

• Record Type: Journal Article
• Authors: Liao, Qinghua; Owen, Michael C.; Bali, Sofia; Barz, Bogdan; Strodel, Birgit
• Is Part Of: Chemical communications. Volume 54:Issue 56(2018)
• Page Start: 7766
• Page End: 7769
• Publication Date: 2018-06-27
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c8cc02263a
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : In light of the high affinity of Cu 2+ for Alzheimer's Aβ1–42 and its ability to subsequently catalyze the formation of radicals, we examine the effects of Cu 2+ binding, Aβ oxidation, and an acidic environment on the conformational dynamics of the smallest Aβ1–42 oligomer, the Aβ1–42 dimer. Abstract : In light of the high affinity of Cu 2+ for Alzheimer's Aβ1–42 and its ability to subsequently catalyze the formation of radicals, we examine the effects of Cu 2+ binding, Aβ oxidation, and an acidic environment on the conformational dynamics of the smallest Aβ1–42 oligomer, the Aβ1–42 dimer. Transition networks calculated from Hamiltonian replica exchange molecular dynamics (H-REMD) simulations reveal that the decreased pH considerably increased the β-sheet content, whereas Cu 2+ binding increased the exposed hydrophobic surface area, both of which can contribute to an increased oligomerization propensity and toxicity.