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

Alba Di Pardo, Vittorio Maglione, Melanie Alpaugh, Melanie Horkey, Randy S. Atwal, Jenny Sassone, Andrea Ciammola, Joan S. Steffan, Karim Fouad, Ray Truant, Simonetta Sipione

Research output: Contribution to journalArticlepeer-review

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 forHDthat targets a posttranslational modification of mutant huntingtin with critical effects on disease pathogenesis.

Original languageEnglish
Pages (from-to)3528-3533
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number9
DOIs
Publication statusPublished - Feb 28 2012

ASJC Scopus subject areas

  • General

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