Neuroprotective Ganglioside Derivatives
Abstract
In this study, neuroprotective ganglioside derivatives are studied in an attempt to devise neuroprotective agents targeted to specific points in cell death pathways. GMl ganglioside and several of its chemically modified derivatives are neuroprotective in a variety of neurotoxic models. Here, ganglioside functional groups required for neuroprotection and blood-brain barrier (BBB) permeance are determined. Cell death mechanisms are also defined, as are the mechanism(s) by which ganglioside derivatives intervene in the cell death process. In the third year, syntheses of various ganglioside derivatives have been accomplished. A significant delay in the proposed work was encountered, however, when a commercial reagent was acidic beyond specifications and, therefore, decomposed the lysoGM1 derivative that is also the starting material for many of the other derivatives. Negotiations are currently underway to determine company culpability and fair replacement. Fatty acid derivatives of GMl have been tested in the SH-SY5y cell culture system. LysoGM1, LIGA 20, N-butylGMl, N-MyristylGMl, and GMl inner ester were all cytoprotective but at different effective concentrations. AsialoGM1 was not cytoprotective.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA428457
Entities
People
- M. D. Ullman
Organizations
- University of Massachusetts