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Lim, Mi Hee
MetalloNeuroChemistry Lab (MNCL)
Research Interests
  • Neurodegenerative disease, small molecule design, network between metal, proteins, and ROS

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Reactivity of Metal-Free and Metal-Associated Amyloid-β with Glycosylated Polyphenols and Their Esterified Derivatives

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Title
Reactivity of Metal-Free and Metal-Associated Amyloid-β with Glycosylated Polyphenols and Their Esterified Derivatives
Author
Korshavn, Kyle J.Jang, MilimKwak, Yeon JuKochi, AkikoVertuani, SilviaBhunia, AnirbanManfredini, StefanoRamamoorthy, AyyalusamyLim, Mi Hee
Issue Date
2015-12
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v.5, pp.17842
Abstract
Both amyloid-β (Aβ) and transition metal ions are shown to be involved in the pathogenesis of Alzheimer’s disease (AD), though the importance of their interactions remains unclear. Multifunctional molecules, which can target metal-free and metal-bound Aβ and modulate their reactivity (e.g., Aβ aggregation), have been developed as chemical tools to investigate their function in AD pathology; however, these compounds generally lack specificity or have undesirable chemical and biological properties, reducing their functionality. We have evaluated whether multiple polyphenolic glycosides and their esterified derivatives can serve as specific, multifunctional probes to better understand AD. The ability of these compounds to interact with metal ions and metal-free/-associated Aβ, and further control both metal-free and metal-induced Aβ aggregation was investigated through gel electrophoresis with Western blotting, transmission electron microscopy, UV-Vis spectroscopy, fluorescence spectroscopy, and NMR spectroscopy. We also examined the cytotoxicity of the compounds and their ability to mitigate the toxicity induced by both metal-free and metal-bound Aβ. Of the polyphenols investigated, the natural product (Verbascoside) and its esterified derivative (VPP) regulate the aggregation and cytotoxicity of metal-free and/or metal-associated Aβ to different extents. Our studies indicate Verbascoside represents a promising structure for further multifunctional tool development against both metal-free Aβ and metal-Aβ.
URI
https://scholarworks.unist.ac.kr/handle/201301/17989
URL
http://www.nature.com/articles/srep17842
DOI
10.1038/srep17842
ISSN
2045-2322
Appears in Collections:
PHY_Journal Papers
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