title: Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor.
abstract: Cucurbit[7]uril (CB[7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP(+) (N-methyl-4-phenylpyridine). The CB[7]/neurotoxin host-guest complexes were studied in detail with (1)H NMR, electrospray ionization mass spectrometry, UV-visible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP(+), respectively, by CB[7] in aqueous solutions with relatively strong affinities and 1:1 host-guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP(+) induced neurodegeneration (often referred to as a Parkinson's disease model) was observed to be strongly inhibited in vivo by the synthetic CB[7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Shengke
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Huanxian
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Aix-Marseille Université , CNRS, Institut de Chimie Radicalaire, UMR 7273, 13013 Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Bardelang
authors.affiliation: Department of Chemistry, Queen's University , Kingston, ON K7L 3N6, Canada.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Wyman
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Simon M Y
authors.initials: SM
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Wang
keywords: Neurodegeneration; cucurbituril; inhibition; neurotoxin; supramolecular complexation