Amylin, amyloid beta (Aβ), and α-synuclein are peptides and proteins that belong to a large family of amyloids, which are involved in the progress of amyloidogenic diseases: amylin in type 2 diabetes, Aβ in Alzheimer's disease, and α-synuclein in Parkinson's disease. Amyloids self-assemble to form aggregates such as oligomers and fibrils. It is known that the amyloid oligomers are the toxic species in these diseases. It is also well documented that metal ions interact with these amyloids to enhance the formation of amyloid oligomers. However, the mechanisms that allow metal ions to interact with these amyloid oligomers are elusive. Thus, to obtain insights into these mechanisms, it is necessary to determine the atomic structures of metal-full-length amyloid oligomer complexes. There many challenges when using current conventional experimental tools to observe the structures of metal-full-length amyloid oligomer complexes at atomic resolution. However, current and future computational studies may help to elucidate the various conformations of metal-full-length amyloid oligomer complexes. This review describes the challenges that must be addressed in experimental and computational studies to obtain a more complete understanding of the mechanisms that allow metal ions bind to these amyloid oligomers.
|Number of pages||7|
|Journal||Coordination Chemistry Reviews|
|State||Published - 15 Nov 2016|
Bibliographical noteFunding Information:
This study was funded by the FP7-PEOPLE-2011-CIG (CIG No. 303741 ) and partly supported by the Israel Science Foundation (grant No. 532/15 ). The studies described include simulations performed using the high-performance computational facilities of the Miller lab in the BGU HPC computational center and partially with the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD ( https://hpc.nih.gov/ ). The support of the BGU HPC computational center staff is greatly appreciated.
© 2016 Elsevier B.V.
- Alzheimer's disease
- Amyloid mechanism
- Amyloid structural oligomer
- Parkinson's disease
- Type 2 diabetes