Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor

摘要

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]eurotoxin host-guest complexes were studied in detail with H-1 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.