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  • Glycolipid and ganglioside metabolism imbalances in Huntington's disease.

    Neurobiol Dis. 27(3):265-77. doi: 10.1016/j.nbd.2007.05.003. September 2007. View on PubMed.
  • Authors

    Desplats PA, Denny CA, Kass KE, Gilmartin T, Head SR, Sutcliffe JG, Seyfried TN, and Thomas EA
  • Abstract

    We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington's disease (HD) mice using a custom-designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD subjects. Many of these genes show differential regional expression within the CNS, as indicated by in situ hybridization analysis, suggesting region-specific regulation of this system in the brain. We further show disrupted patterns of glycolipids (acidic and neutral lipids) and/or ganglioside levels in both the forebrain of the R6/1 transgenic mice and caudate samples from human HD subjects. These findings reveal novel disruptions in glycolipid/ganglioside metabolic pathways in the pathology of HD and suggest that the development of new targets to restore glycosphingolipid balance may act to ameliorate some symptoms of HD.

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