The Aggregation Pattern of Aβ 1–40 is Altered by the Presence of N ‐Truncated Aβ 4–40 and/or Cu II in a Similar Way through Ionic Interactions - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Chemistry - A European Journal Année : 2021

The Aggregation Pattern of Aβ 1–40 is Altered by the Presence of N ‐Truncated Aβ 4–40 and/or Cu II in a Similar Way through Ionic Interactions

Résumé

Alzheimer's disease (AD) is one of the most common of the multifactorial diseases and is characterized by a range of abnormal molecular processes, such as the accumulation of extracellular plaques containing the amyloid‐β (Aβ) peptides and dyshomeostasis of copper in the brain. In this study, we have investigated the effect of CuII on the aggregation of Aβ1–40 and Aβ4–40, representing the two most prevalent families of Aβ peptides, that is, the full length and N‐truncated peptides. Both families are similarly abundant in healthy and AD brains. For either of the studied peptides, substoichiometric CuII concentrations accelerated aggregation, whereas superstoichiometric CuII inhibited fibril formation, likely by stabilizing the oligomers. The addition of either Aβ4–40 or substoichiometric CuII affected the aggregation profile of Aβ1–40, by yielding shorter and thicker fibrils; amorphous aggregates were formed in the presence of a molar excess of CuII. The similarity of these two effects can be attributed to the increase in the positive charge on the Aβ N terminus, caused both by CuII complexation and N truncation at position 4. Our findings provide a better understanding of the biological Aβ aggregation process as these two Aβ species and CuII coexist and interact under physiological conditions.
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Dates et versions

hal-03203165 , version 1 (20-04-2021)

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Ewelina Stefaniak, Elena Atrián-Blasco, Wojciech Goch, Laurent Sabater, Christelle Hureau, et al.. The Aggregation Pattern of Aβ 1–40 is Altered by the Presence of N ‐Truncated Aβ 4–40 and/or Cu II in a Similar Way through Ionic Interactions. Chemistry - A European Journal, 2021, 27 (8), pp.2798-2809. ⟨10.1002/chem.202004484⟩. ⟨hal-03203165⟩
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