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首页> 美国政府科技报告 >Neuroprotective Ganglioside Derivatives
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Neuroprotective Ganglioside Derivatives

机译：神经保护神经节苷脂衍生物

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TTNatural and semisynthetic gangliosides protect neurons from toxin- induced cell death and salvage neurons after toxin exposure. The hydrophilic property of gangliosides restricts their blood-brain barrier (BBB) permeability, which hinders their use as neuroprotective agents. Gangliosides semisynthetic derivatives with improved cytoprotective properties and BBB permeability can be produced. Even with gangliosides great therapeutic promise, no study has examined ganglioside functional group derivatives that would provide cytoprotection AND effectively cross the BBB; information that would provide a basis for future studies of neuroprotective mechanisms. This study examined the ability of ganglioside derivatives to be cytoprotective in vitro models using the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+) and the SH-SY5Y cell line. Derivatives determined to have therapeutic potential were to be tested in vitro for their ability to cross a brain capillary endothelial cell culture model of the BBB. Finally, derivatives that were both cytoprotective and that effectively crossed the in vitro BBB model were to be tested in vivo for their ability to neuroprotect dopaminergic neurons in both chronic and acute neurotoxicity models using the MPP+ precursor, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). The hypothesis is that changes in ganglioside ceramide and/or oligosaccharide functional groups can improve neuroprotection through changes in cytoprotection and BBB transcytosis.

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