Amylin–Aβ oligomers at atomic resolution using molecular dynamics simulations: a link between Type 2 diabetes and Alzheimer's disease. Issue 4 (9th September 2015)

• Record Type: Journal Article
• Authors: Baram, Michal; Atsmon-Raz, Yoav; Ma, Buyong; Nussinov, Ruth; Miller, Yifat
• Is Part Of: Physical chemistry chemical physics. Volume 18:Issue 4(2016)
• Page Start: 2330
• Page End: 2338
• Publication Date: 2015-09-09
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/c5cp03338a
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : Aβ1–42 oligomers prefer to interact with Amylin1–37 oligomers to form single layer conformations. Abstract : Clinical studies have identified Type 2 diabetes (T2D) as a risk factor of Alzheimer's disease (AD). One of the potential mechanisms that link T2D and AD is the loss of cells associated with degenerative changes. Amylin1–37 aggregates (the pathological species in T2D) were found to be co-localized with those of Aβ1–42 (the pathological species in AD) to form the Amylin1–37 –Aβ1–42 plaques, promoting aggregation and thus contributing to the etiology of AD. However, the mechanisms by which Amylin1–37 co-aggregates with Aβ1–42 are still elusive. This work presents the interactions between Amylin1–37 oligomers and Aβ1–42 oligomers at atomic resolution applying extensive molecular dynamics simulations for relatively large ensemble of cross-seeding Amylin1–37 –Aβ1–42 oligomers. The main conclusions of this study are first, Aβ1–42 oligomers prefer to interact with Amylin1–37 oligomers to form single layer conformations (in-register interactions) rather than double layer conformations; and second, in some double layer conformations of the cross-seeding Amylin1–37 –Aβ1–42 oligomers, the Amylin1–37 oligomers destabilize the Aβ1–42 oligomers and thus inhibit Aβ1–42 aggregation, while in other double layer conformations, the Amylin1–37 oligomers stabilize Aβ1–42 oligomers and thus promote Aβ1–42 aggregation.