期刊
ACS CHEMICAL NEUROSCIENCE
卷 4, 期 11, 页码 1488-1500出版社
AMER CHEMICAL SOC
DOI: 10.1021/cn400141x
关键词
Amyloid oligomer; water channel; molecular dynamics; crosses seeding
资金
- National Institutes of Health [GM62838]
- Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231]
- Hacetttepe University [012.D12.602.001]
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.
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