In Silico Cross Seeding of A beta and Amylin Fibril-like Oligomers

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Berhanu W. M., Yasar F., Hansmann U. H. E.

ACS CHEMICAL NEUROSCIENCE, vol.4, no.11, pp.1488-1500, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 4 Issue: 11
  • Publication Date: 2013
  • Doi Number: 10.1021/cn400141x
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1488-1500
  • Hacettepe University Affiliated: Yes


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 beta and amylin. Because the resulting amyloid oligomers are difficult to probe in experiments, we investigate stability and conformational changes of A beta amylin heteroassemblies through molecular dynamics simulations. We find that A beta is a good template for the growth of amylin and vice versa. We see water molecules permeate the beta-strand-turn-beta-strand motif pore of the oligomers, supporting a commonly accepted mechanism for toxicity of A beta-rich amyloid oligomers. Aiming for a better understanding of the physical mechanisms of cross-seeding and cell toxicity of amylin and A beta aggregates, our simulations also allow us to identify targets for the rational design of inhibitors against toxic fibril-like oligomers of A beta and amylin oligomers.