Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies
Alzheimer’s disease (AD) and type 2 diabetes (T2D) are two common protein aggregation diseases. Compelling evidence has shown a link between AD and T2D, which may derive from interspecies cross-sequence interactions between amyloid-β peptide (Aβ), associated with AD, and human islet amyloid polypeptide (hIAPP), associated with T2D. Herein, we present experimental and computational protocols and tools to study the aggregate structures and kinetics, conformational conversion, and molecular interactions of Aβ-hIAPP mixtures. These protocols could be generally applied to other cross-seeding behaviors of amyloid peptides.
Key wordsAmyloid peptides Aβ hIAPP Cross-seeding Alzheimer disease Diabetes
J.Z. thanks the financial support from NSF (CBET-1510099 and DMR-1607475), Alzheimer Association (2015-NIRG-341372), and National Natural Science Foundation of China (NSFC-21528601). The high-performance computational facilities of the Biowulf PC/Linux cluster at the NIH were mainly used for the simulations. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
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