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In silico cross seeding of A? and amylin fibril-like oligomers.

ABSTRACT: Recent epidemiological data have shown that patients suffering from Type 2 Diabetes Mellitus have an increased risk to develop Alzheimer's disease and vice versa. A possible explanation is the cross-sequence interaction between A? and amylin. Because the resulting amyloid oligomers are difficult to probe in experiments, we investigate stability and conformational changes of A?-amylin heteroassemblies through molecular dynamics simulations. We find that A? is a good template for the growth of amylin and vice versa. We see water molecules permeate the ?-strand-turn-?-strand motif pore of the oligomers, supporting a commonly accepted mechanism for toxicity of ?-rich amyloid oligomers. Aiming for a better understanding of the physical mechanisms of cross-seeding and cell toxicity of amylin and A? aggregates, our simulations also allow us to identify targets for the rational design of inhibitors against toxic fibril-like oligomers of A? and amylin oligomers.

SUBMITTER: Berhanu WM

PROVIDER: S-EPMC3837374 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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In silico cross seeding of Aβ and amylin fibril-like oligomers.

Berhanu Workalemahu M WM Yaşar Fatih F Hansmann Ulrich H E UH

ACS chemical neuroscience 20130919 11

Recent epidemiological data have shown that patients suffering from Type 2 Diabetes Mellitus have an increased risk to develop Alzheimer's disease and vice versa. A possible explanation is the cross-sequence interaction between Aβ and amylin. Because the resulting amyloid oligomers are difficult to probe in experiments, we investigate stability and conformational changes of Aβ-amylin heteroassemblies through molecular dynamics simulations. We find that Aβ is a good template for the growth of amy ...[more]

PMID: 24007594

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