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


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 A?1-42 (the pathological species in AD) to form the Amylin1-37-A?1-42 plaques, promoting aggregation and thus contributing to the etiology of AD. However, the mechanisms by which Amylin1-37 co-aggregates with A?1-42 are still elusive. This work presents the interactions between Amylin1-37 oligomers and A?1-42 oligomers at atomic resolution applying extensive molecular dynamics simulations for relatively large ensemble of cross-seeding Amylin1-37-A?1-42 oligomers. The main conclusions of this study are first, A?1-42 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-A?1-42 oligomers, the Amylin1-37 oligomers destabilize the A?1-42 oligomers and thus inhibit A?1-42 aggregation, while in other double layer conformations, the Amylin1-37 oligomers stabilize A?1-42 oligomers and thus promote A?1-42 aggregation.

SUBMITTER: Baram M 

PROVIDER: S-EPMC4720542 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Baram Michal M   Atsmon-Raz Yoav Y   Ma Buyong B   Nussinov Ruth R   Miller Yifat Y  

Physical chemistry chemical physics : PCCP 20160101 4


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-  ...[more]

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