Glycolipid and ganglioside metabolism imbalances in Huntington's disease

Neurobiol Dis. 2007 Sep;27(3):265-77. doi: 10.1016/j.nbd.2007.05.003. Epub 2007 May 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / metabolism*
  • Gangliosides / metabolism*
  • Gene Expression
  • Glycolipids / metabolism*
  • Glycosyltransferases / genetics*
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • In Situ Hybridization
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction


  • Gangliosides
  • Glycolipids
  • RNA, Messenger
  • Glycosyltransferases