Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 142, Issue -, Pages 265-276Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2019.09.098
Keywords
Alzheimer's disease; Chondroitin sulfate; Selenium; Multi-target; Tau; Amyloids
Funding
- Natural Science Foundation of China [81671395]
- Projects of Medical and Health Technology Development Program in Shandong Province [2016WS0610]
- Natural Science Foundation of Shandong Province of China [ZR2016HM40]
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The purpose of this study was to ascertain the effect of selenium-chondroitin sulfate nanoparticles (CS@Se) on multi-target-directed therapy for the treatment of Alzheimer's disease (AD). CS@Se nanoparticles were successfully synthesized, and their therapeutic effects were studied in in vitro AD models. CS@Se effectively inhibited amyloid-beta (A beta) aggregation and protected SH-SY5Y cells from A beta(1-42)- induced cytotoxicity. Moreover, CS@Se significantly decreased okadaic acid-induced actin cytoskeleton instability in SH-SY5Y cells. In addition, CS@Se decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the levels of glutathione peroxidase (GSH-Px). The Western blot results indicated that CS@Se attenuated the hyperphosphorylation of tau (Ser396/Ser404) by regulating the expression of GSK-3 beta. In summary, this study demonstrated that CS@Se could inhibit the aggregation of A beta, reduce damage to the cytoskeleton, mitigate oxidative stress and attenuate the hyperphosphorylation of tau protein. CS@Se might be a potent multi-functional agent for the treatment of AD and thus warrants further research and evaluation. (C) 2019 Elsevier B.V. All rights reserved.
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