Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila

Nature
J S SteffanL M Thompson

Abstract

Proteins with expanded polyglutamine repeats cause Huntington's disease and other neurodegenerative diseases. Transcriptional dysregulation and loss of function of transcriptional co-activator proteins have been implicated in the pathogenesis of these diseases. Huntington's disease is caused by expansion of a repeated sequence of the amino acid glutamine in the abnormal protein huntingtin (Htt). Here we show that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly binds the acetyltransferase domains of two distinct proteins: CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF). In cell-free assays, Httex1p also inhibits the acetyltransferase activity of at least three enzymes: p300, P/CAF and CBP. Expression of Httex1p in cultured cells reduces the level of the acetylated histones H3 and H4, and this reduction can be reversed by administering inhibitors of histone deacetylase (HDAC). In vivo, HDAC inhibitors arrest ongoing progressive neuronal degeneration induced by polyglutamine repeat expansion, and they reduce lethality in two Drosophila models of polyglutamine disease. These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neuro...Continue Reading

References

Jan 1, 1982·Molecular & General Genetics : MGG·G ReuterH J Hoffmann
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·S T SuhrF H Gage
Aug 1, 1998·Nucleic Acids Research·S Ait-Si-AliA Harel-Bellan
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·E ScherzingerE E Wanker
Sep 25, 1999·Journal of Cellular Physiology·A Giordano, M L Avantaggiati
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KazantsevD Housman
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·J S SteffanL M Thompson
Jun 9, 2000·Annual Review of Neuroscience·H Y Zoghbi, H T Orr
Aug 3, 2000·Journal of the National Cancer Institute·P A MarksR A Rifkind
Aug 15, 2000·Trends in Neurosciences·J H Cha
Aug 25, 2000·Human Molecular Genetics·A McCampbellK H Fischbeck

❮ Previous
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Citations

Jul 29, 2010·EMBO Molecular Medicine·Stephen J McConougheyRajiv R Ratan
Mar 11, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Motomasa TanakaNobuyuki Nukina
Mar 27, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gregor P Lotz, Justin Legleiter
Apr 6, 2012·Cell and Tissue Research·Haruhiko BannoGen Sobue
Jul 3, 2009·Molecules and Cells·Seongman Kang, Sunghoi Hong
Sep 6, 2011·Functional & Integrative Genomics·Ehsan HabibiStephen J Haggarty
Jun 18, 2010·Journal of Bioenergetics and Biomembranes·Youngnam N Jin, Gail V W Johnson
Jun 5, 2002·Current Neurology and Neuroscience Reports·Susan L Perlman
Jul 11, 2006·Current Neurology and Neuroscience Reports·Sarah B Berman, J Timothy Greenamyre
May 21, 2013·Cell Biochemistry and Biophysics·He HuangMaria E Figueiredo-Pereira
Jun 7, 2008·Journal of Biosciences·Sonali Sengupta, Subramaniam Ganesh
Apr 18, 2008·The Cerebellum·Benjamin R Underwood, David C Rubinsztein
Nov 6, 2009·The Cerebellum·Antoni Matilla-DueñasPilar Latorre
Mar 24, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Michelle E Ehrlich
Mar 19, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·H Akiko PopielYoshitaka Nagai
May 24, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Barbara CalaminiLinda S Kaltenbach
Sep 6, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anne SchneiderAnne-Laurence Boutillier
Sep 6, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Junghee LeeHoon Ryu
May 10, 2005·Bioorganic & Medicinal Chemistry·K VanommeslaegheP Geerlings
Apr 9, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Steven M Hersch, H Diana Rosas
Aug 25, 2012·Journal of the American Chemical Society·Reisuke BabaKazuya Kikuchi
Jan 11, 2011·Cell Death and Differentiation·P RichardsP Nicotera
Mar 27, 2010·Cell Death and Differentiation·I NisoliB Charroux
Nov 11, 2011·Cell Death & Disease·D BanoP Nicotera
Sep 7, 2013·Experimental & Molecular Medicine·Arulmani ManavalanKlaus Heese
Jun 17, 2008·Nature Cell Biology·Nilkantha SenAkira Sawa
Apr 9, 2008·Nature Chemical Biology·Andrea WilliamsDavid C Rubinsztein
Aug 26, 2006·Nature Clinical Practice. Neurology·Ghazaleh Sadri-Vakili, Jang-Ho J Cha
Aug 27, 2013·Nature Genetics·Robert P MasonFlaviano Giorgini
Aug 8, 2012·Nature Medicine·Mira Jakovcevski, Schahram Akbarian
Jan 9, 2010·Nature Medicine·Cassandra Willyard
May 2, 2002·Nature Medicine·Ted M Dawson, David D Ginty
Jul 24, 2004·Nature Medicine·Ella Bossy-WetzelStuart A Lipton
Dec 17, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lei WangLan Ma
Jun 14, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Iva B Zovkic, J David Sweatt
Jun 7, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lucia Peixoto, Ted Abel
Oct 2, 2008·Nature Reviews. Drug Discovery·Aleksey G Kazantsev, Leslie M Thompson
Jan 5, 2005·Nature Reviews. Genetics·Ethan Bier

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