title: Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice.
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.
authors.affiliation: Department of Pharmacology,  University of Alberta, Edmonton, AB,  Canada T6G 2H7.
authors.forename: Alba
authors.initials: A
authors.lastname: Di Pardo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Maglione
authors.forename: Melanie
authors.initials: M
authors.lastname: Alpaugh
authors.forename: Melanie
authors.initials: M
authors.lastname: Horkey
authors.forename: Randy S
authors.initials: RS
authors.lastname: Atwal
authors.forename: Jenny
authors.initials: J
authors.lastname: Sassone
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciammola
authors.forename: Joan S
authors.initials: JS
authors.lastname: Steffan
authors.forename: Karim
authors.initials: K
authors.lastname: Fouad
authors.forename: Ray
authors.initials: R
authors.lastname: Truant
authors.forename: Simonetta
authors.initials: S
authors.lastname: Sipione
mesh_terms: D000818:Animals; D003062:Codon / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D019281:Dimerization; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000096:biosynthesis / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000627:therapeutic use*; D000071058:Huntingtin Protein; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000032:analysis; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects
chemical_list: D003062:Codon; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C497929:Ppp1r1b protein, mouse; D010768:Phosphoserine; D005677:G(M1) Ganglioside