Neuroprotective Ganglioside Derivatives
Abstract
In this study, neuroprotective ganglioside derivatives are examined so they can be targeted to specific points in cell death pathways. Here, ganglioside functional groups required for neuroprotection and blood-brain barrier permeance are determined. Cell death mechanisms and the mechanism(s) by which semisynthetic gangliosides intervene in the cell death process are also studied. In the second year C2, C4, CS, C14, C20, and C26 fatty acid GMl derivatives were synthesized. Experiments on semisynthetic ganglioside cytoprotection using a retinoic acid- differentiated SH-SY5Y human neuroblastoma cell/MPP+ model have been initiated. Each derivative requires analysis at different concentrations and preincubation times. Of the compounds studied to date (C2GM1, dichloroC2GM1, C4GM1, Cl4GM1), the C4GM1 derivative is the most cytoprotective, being 1.4 times more effective than the+ parent GM1. cDNA microarray analysis of changes in gene expression associated with MPP toxicity revealed that MPP+ exposure resulted in decreased RMB3 expression, increased GADD153 expression, and increased c-Myc expression. Further findings suggest that increased pancreatic protein disulfide isomerase (PDIp) expression in MPP+ stressed SH-SY5Y cells may promote Lewy body formation and perhaps contribute to neurotoxicity and neurodegeneration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA420111
Entities
People
- M. D. Ullman
Organizations
- University of Massachusetts Medical School