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Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3528-33. doi: 10.1073/pnas.1114502109. Epub 2012 Feb 13.

Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice.

Author information

  • 1Department of Pharmacology, University of Alberta, Edmonton, AB, Canada T6G 2H7.

Abstract

Huntington disease (HD) is a progressive neurodegenerative monogenic disorder caused by expansion of a polyglutamine stretch in the huntingtin (Htt) protein. Mutant huntingtin triggers neural dysfunction and death, mainly in the corpus striatum and cerebral cortex, resulting in pathognomonic motor symptoms, as well as cognitive and psychiatric decline. Currently, there is no effective treatment for HD. We report that intraventricular infusion of ganglioside GM1 induces phosphorylation of mutant huntingtin at specific serine amino acid residues that attenuate huntingtin toxicity, and restores normal motor function in already symptomatic HD mice. Thus, our studies have identified a potential therapy for HD that targets a posttranslational modification of mutant huntingtin with critical effects on disease pathogenesis.

PMID:
22331905
[PubMed - indexed for MEDLINE]
PMCID:
PMC3295265
Free PMC Article

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