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

Proceedings of the National Academy of Sciences of the United States of America
Alba Di PardoSimonetta Sipione

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.

References

Jul 21, 1998·Annals of the New York Academy of Sciences·J S Schneider
Jul 21, 1998·Annals of the New York Academy of Sciences·M Alter
Jun 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·J A BibbP Greengard
Nov 14, 2000·Brain Research·G A MetzK Fouad
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·K Simons, D Toomre
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sen-itiroh Hakomori Si
Sep 10, 2002·Dementia and Geriatric Cognitive Disorders·Lars SvennerholmCarsten Wikkelsö
Jun 10, 2003·Journal of Molecular Neuroscience : MN·Janet L OblingerRichard W Burry
Jun 19, 2003·Human Molecular Genetics·Elizabeth J SlowMichael R Hayden
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Per SvenningssonPaul Greengard
Apr 6, 2004·Science·Joan S SteffanJ Lawrence Marsh
Feb 16, 2005·The Journal of Biological Chemistry·Marcos S ToledoSenitiroh Hakomori
Apr 23, 2005·The Cochrane Database of Systematic Reviews·P Chinnock, I Roberts
Sep 15, 2005·Cellular and Molecular Life Sciences : CMLS·I Mocchetti
Nov 9, 2005·Mechanisms of Ageing and Development·Ferdinando SquitieriOliver Quarrell
Apr 6, 2006·The Journal of Biological Chemistry·Wei LiJames A Huntington
Jun 20, 2006·The Journal of Biological Chemistry·Birgit SchillingLisa M Ellerby
Sep 20, 2006·Glycobiology·Sandro SonninoAlessandro Prinetti
Dec 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Seon-Joo YoonSen-itiroh Hakomori
Jun 30, 2007·Neurobiology of Disease·Paula A DesplatsElizabeth A Thomas
Jul 6, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sandrine L AnneSandrine Humbert
Nov 21, 2007·Expert Opinion on Therapeutic Targets·Helton J ReisMarco A Romano-Silva
Feb 9, 2008·Neurobiology of Aging·Alexandra BernardoMichael P McDonald
Mar 11, 2008·Journal of Lipid Research·Robert W Ledeen, Gusheng Wu
Nov 11, 2008·Molecular and Cellular Neurosciences·Simon C WarbyMichael R Hayden
Mar 10, 2009·Nature Structural & Molecular Biology·Ashwani K ThakurRonald Wetzel
Mar 14, 2009·PLoS Computational Biology·Gareth A PalidworMiguel A Andrade-Navarro
Apr 7, 2009·Cell·Hyunkyung JeongDimitri Krainc
Jun 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Gusheng WuRobert W Ledeen
Aug 28, 2009·The Journal of Biological Chemistry·Charity T AikenJ Lawrence Marsh
Sep 8, 2009·Biochimica Et Biophysica Acta·Jacques Fantini, Francisco J Barrantes
Oct 14, 2009·FEBS Letters·Ronald L Schnaar
Dec 17, 2009·FEBS Letters·Elena Posse de Chaves, Simonetta Sipione
Dec 23, 2009·The Journal of Cell Biology·Leslie Michels ThompsonJoan S Steffan
Mar 9, 2010·Journal of the Neurological Sciences·Jay S SchneiderFranca Cambi
Mar 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Vittorio MaglioneSimonetta Sipione
May 6, 2010·PLoS Computational Biology·Vinal V LakhaniNikolay V Dokholyan

❮ Previous
Next ❯

Citations

Sep 5, 2012·Molecular Neurobiology·Pawel M SwitonskiMaciej Figiel
Apr 19, 2012·The Journal of Biological Chemistry·Ningzhe ZhangLisa M Ellerby
Feb 8, 2014·PloS One·Erin E WatkinChristopher A Ross
Nov 22, 2012·Cancer Informatics·Michael L Bittner, Edward R Dougherty
Dec 18, 2013·Human Molecular Genetics·Nicholas S CaronRay Truant
Jun 25, 2015·Biochemical and Biophysical Research Communications·Maria Blaire BustamanteAndrea Caricasole
Jun 7, 2014·Journal of Neuroscience Research·Toshio Ariga
Aug 27, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Edward J Wild, Sarah J Tabrizi
Aug 1, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Kathleen M Shannon, Avram Fraint
May 7, 2013·Biochimica Et Biophysica Acta·Kathleen A BurkeJustin Legleiter
May 31, 2015·Trends in Biochemical Sciences·Robert W Ledeen, Gusheng Wu
May 6, 2015·Der Nervenarzt·J D Rollnik
Jun 12, 2013·Communicative & Integrative Biology·Carly R DesmondRay Truant
Aug 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Flaviano Giorgini
Jul 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nicholas Stephane CaronRay Truant
Oct 14, 2014·Frontiers in Cellular Neuroscience·Robert BrunkhorstWaltraud Pfeilschifter
Aug 2, 2016·Orphanet Journal of Rare Diseases·Eleni MinaMarco Roos
Aug 16, 2016·The Journal of Clinical Investigation·Ian H KratterSteven Finkbeiner
May 22, 2016·The International Journal of Neuropsychopharmacology·Bo JiangLi-Juan Tong
Oct 19, 2016·International Journal of Molecular Sciences·Domenico RussoGiovanni D'Angelo
Dec 27, 2016·Human Molecular Genetics·Tamara MaiuriRay Truant
Feb 9, 2017·Biochemistry·Adewale AdegbuyiroJustin Legleiter
Oct 22, 2016·Neurochemical Research·Mercedes Garcia-Gil, Elisabetta Albi
May 17, 2017·Chemical Communications : Chem Comm·Kyan A D'Angelo, Mark S Taylor
Dec 7, 2017·Translational Neurodegeneration·Sebastian AguiarFrancesco Albert Bosco Cortese
Nov 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Cristina CariuloAndrea Caricasole
Jul 19, 2018·Journal of Neuroscience Research·Nate Pappenhagen, Denise M Inman
Sep 22, 2018·Nature Reviews. Drug Discovery·Nicholas S CaronMichael R Hayden
Sep 27, 2018·Molecular Biology of the Cell·Claudia Lin-Kar HungRay Truant
Jan 1, 2015·Nature Reviews. Disease Primers·Gillian P BatesSarah J Tabrizi
Oct 11, 2017·EMBO Molecular Medicine·Melanie AlpaughSimonetta Sipione
Mar 6, 2015·Biomolecular Concepts·James R ArndtJustin Legleiter
Jul 1, 2014·Current Opinion in Neurology·Samuel D Kim, Victor S C Fung
May 14, 2020·Journal of Neurochemistry·Manal AlaameryFrancisco J Quintana

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.