Journal
NATIONAL SCIENCE REVIEW
Volume 7, Issue 4, Pages 763-774Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nsr/nwz215
Keywords
gold nanoclusters; Alzheimer's disease; restores fibril A beta's unfolded state; abolished cytotoxicity; dissolves endogenous A beta plaques
Categories
Funding
- National Natural Science Foundation of China [21975191, 21805218, 51873168, 81803515, 51533007, 51521001]
- Natural Science Foundation of Hubei Province [2018CFA002, 2018CFB348]
- Wuhan University of Technology [472-20162008]
- Fundamental Research Funds for the Central Universities [WUT: 2018III023]
- Excellent Dissertation Cultivation Funds of Wuhan University of Technology [2017-YS-010]
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The misfolding of amyloid-beta (A beta) peptides from the natural unfolded state to beta-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous A beta plaques in Alzheimer's disease (AD). Previous studies have reported inhibition of A beta fibrillation or disassembly of exogenous A beta fibrils in vitro. However, soluble A beta oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of A beta fibrils by anti-A beta antibodies have failed so far. Here we show that Au-23(CR)(14) (a new Au nanocluster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature A beta fibrils into monomers and restore the natural unfolded state of A beta peptides from misfolded beta-sheets. Furthermore, the cytotoxicity of A beta(40) fibrils when dissolved by Au-23(CR)(14) is fully abolished. More importantly, Au-23(CR)(14) is able to completely dissolve endogenous A beta plaques in brain slices from transgenic AD model mice. In addition, Au-23(CR)(14) has good biocompatibility and infiltration ability across the blood-brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines.
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