title: Reactivity of Metal-Free and Metal-Associated Amyloid-β with Glycosylated Polyphenols and Their Esterified Derivatives.
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.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Korshavn
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
authors.forename: Milim
authors.initials: M
authors.lastname: Jang
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
authors.forename: Yeon Ju
authors.initials: YJ
authors.lastname: Kwak
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, United States.|Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kochi
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vertuani
authors.affiliation: Biophysics, University of Michigan, Ann Arbor, Michigan 48109-1055, United States.|Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII(M), Kolkata 700054, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Bhunia
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Manfredini
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, United States.|Biophysics, University of Michigan, Ann Arbor, Michigan 48109-1055, United States.
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.affiliation: Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lim
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D008024:Ligands; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D059808:Polyphenols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008024:Ligands; D008670:Metals; D059808:Polyphenols; D066329:Protein Aggregates