Journal article
Spontaneous formation of β-sheet nano-barrels during the early aggregation of Alzheimer's amyloid beta
Y Sun, A Kakinen, X Wan, N Moriarty, CPJ Hunt, Y Li, N Andrikopoulos, A Nandakumar, TP Davis, CL Parish, Y Song, PC Ke, F Ding
Nano Today | ELSEVIER SCI LTD | Published : 2021
Abstract
Soluble low-molecular-weight oligomers formed during the early aggregation of amyloid peptides have been hypothesized as a major toxic species of amyloidogenesis. Herein, we performed the first synergic in silico, in vitro and in vivo validations of the structure, dynamics and toxicity of Aβ42 oligomers. Aβ peptides readily assembled into β-rich oligomers comprised of extended β-hairpins and β-strands. Nanosized β-barrels were observed with certainty with simulations, transmission electron microscopy and Fourier transform infrared spectroscopy, corroborated by immunohistochemistry, cell viability, apoptosis, inflammation, autophagy and animal behavior assays. Secondary and tertiary structura..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported in part by the National Natural Science Foundation of China under the Grant No. 11904189 (Sun), K.C.Wong Magna Fund in Ningbo University, China (Sun), US National Science Foundation CBET-1553945 (Ding), and US National Institutes of Health R35GM119691 (Ding). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NSFC, NIH and NSF. This work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano and microfabrication facilities for Australia's researchers.