Amylin-Aβ oligomers at atomic resolution using molecular dynamics simulations: A link between Type 2 diabetes and Alzheimer's disease

Michal Baram, Yoav Atsmon-Raz, Buyong Ma, Ruth Nussinov, Yifat Miller

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2330-2338
Number of pages9
JournalPhysical Chemistry Chemical Physics
Volume18
Issue number4
DOIs
StatePublished - 28 Jan 2016

Fingerprint

Dive into the research topics of 'Amylin-Aβ oligomers at atomic resolution using molecular dynamics simulations: A link between Type 2 diabetes and Alzheimer's disease'. Together they form a unique fingerprint.

Cite this