Htt

Summary

Gene Symbol: Htt
Description: huntingtin
Alias: AI256365, C430023I11Rik, Hdh, IT15, huntingtin, HD protein homolog, Huntington disease gene homolog, huntington disease protein homolog
Species: mouse

Top Publications

  1. ncbi Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum
    Vanessa C Wheeler
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mol Genet 12:273-81. 2003
  2. ncbi Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice
    L Mangiarini
    Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, United Kingdom
    Cell 87:493-506. 1996
  3. ncbi Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats
    Liliana B Menalled
    Department of Neurology, University of California at Los Angeles, Los Angeles, California 90095, USA
    J Comp Neurol 465:11-26. 2003
  4. ncbi Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice
    K Manley
    Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, New York, USA
    Nat Genet 23:471-3. 1999
  5. ncbi Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes
    Chiara Zuccato
    Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Via Balzaretti 9, 20133 Milano, Italy
    Nat Genet 35:76-83. 2003
  6. ncbi The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes
    Ben Woodman
    Department of Medical and Molecular Genetics, King s College London School of Medicine, London, UK
    Brain Res Bull 72:83-97. 2007
  7. ncbi Neurological abnormalities in a knock-in mouse model of Huntington's disease
    C H Lin
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Hum Mol Genet 10:137-44. 2001
  8. pmc Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease
    Christian Landles
    Department Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London SE1 9RT, United Kingdom
    J Biol Chem 285:8808-23. 2010
  9. ncbi Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation
    S W Davies
    Department of Anatomy and Developmental Biology, University College London, United Kingdom
    Cell 90:537-48. 1997
  10. pmc Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models
    Liliana Menalled
    PsychoGenics Inc, Tarrytown, NY 10591, USA
    Neurobiol Dis 35:319-36. 2009

Research Grants

  1. Does cortex kill striatum in HD?
    CHRISTOPHER MEADE; Fiscal Year: 2004
  2. Neuroprotective Effects of Enhanced Proteasome Function
    BARBARA SNIDER; Fiscal Year: 2006
  3. Combination Drug Therapy in Huntington's Disease
    ROBERT FERRANTE; Fiscal Year: 2008
  4. BIOPHYSICAL STUDY OF ANTIPSYCHOTICS BEHAVIORAL EFFECTS
    Stephen Fowler; Fiscal Year: 2009
  5. NMDA RECEPTOR DEVELOPMENT IN NEOSTRIATUM
    Michael Levine; Fiscal Year: 2001
  6. OXIDATIVE INJURY IN PARKINSONS DISEASE
    ROBERT FERRANTE; Fiscal Year: 2002
  7. 2003 Gordon Conference on CAG Triplet Repeat Disorders
    Michael Levine; Fiscal Year: 2003
  8. 2005 CAG Triplet Repeat Disorders Gordon Conference
    Michael Levine; Fiscal Year: 2005
  9. Modulation of ataxin-1 phosphorylation
    Harry Orr; Fiscal Year: 2006
  10. Embryonic Stem Cell Model of Polyglutamine Disease
    MATTHEW LORINCZ; Fiscal Year: 2007

Scientific Experts

Detail Information

Publications161 found, 100 shown here

  1. ncbi Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum
    Vanessa C Wheeler
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mol Genet 12:273-81. 2003
    Somatic instability of expanded HD CAG repeats that encode the polyglutamine tract in mutant huntingtin has been implicated in the striatal selectivity of Huntington's disease (HD) pathology...
  2. ncbi Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice
    L Mangiarini
    Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, United Kingdom
    Cell 87:493-506. 1996
    ..This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies...
  3. ncbi Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats
    Liliana B Menalled
    Department of Neurology, University of California at Los Angeles, Los Angeles, California 90095, USA
    J Comp Neurol 465:11-26. 2003
    Huntington's disease (HD) is caused by an abnormal expansion of CAG repeats in the gene encoding huntingtin. The development of therapies for HD requires preclinical testing of drugs in animal models that reproduce the dysfunction and ..
  4. ncbi Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice
    K Manley
    Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, New York, USA
    Nat Genet 23:471-3. 1999
    ..9) or an expanded repeat inserted into the endogenous mouse gene Hdh (ref. 10)...
  5. ncbi Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes
    Chiara Zuccato
    Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Via Balzaretti 9, 20133 Milano, Italy
    Nat Genet 35:76-83. 2003
    b>Huntingtin protein is mutated in Huntington disease. We previously reported that wild-type but not mutant huntingtin stimulates transcription of the gene encoding brain-derived neurotrophic factor (BDNF; ref. 2)...
  6. ncbi The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes
    Ben Woodman
    Department of Medical and Molecular Genetics, King s College London School of Medicine, London, UK
    Brain Res Bull 72:83-97. 2007
    ..Of these, mice that are transgenic for an N-terminal huntingtin fragment have been used most extensively because they develop phenotypes with relatively early ages of onset and ..
  7. ncbi Neurological abnormalities in a knock-in mouse model of Huntington's disease
    C H Lin
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Hum Mol Genet 10:137-44. 2001
    ..HD) were made using gene targeting to replace the short CAG repeat of the mouse Huntington's disease gene homolog (HDH:) with CAG repeats within the length range found to cause HD in humans...
  8. pmc Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease
    Christian Landles
    Department Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London SE1 9RT, United Kingdom
    J Biol Chem 285:8808-23. 2010
    b>Huntingtin proteolysis has been implicated in the molecular pathogenesis of Huntington disease (HD). Despite an intense effort, the identity of the pathogenic smallest N-terminal fragment has not been determined...
  9. ncbi Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation
    S W Davies
    Department of Anatomy and Developmental Biology, University College London, United Kingdom
    Cell 90:537-48. 1997
    ..to (CAG)156 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype...
  10. pmc Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models
    Liliana Menalled
    PsychoGenics Inc, Tarrytown, NY 10591, USA
    Neurobiol Dis 35:319-36. 2009
    ..Finally, the Hdh(Q111) knock-in mouse on a CD1 background showed very mild deficits...
  11. ncbi Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis
    Laura Kennedy
    Division of Molecular Genetics, Faculty of Biomedical and Life Scienes, University of Glasgow, Anderson College Complex, 56 Dumbarton Road, Glasgow G11 6NU, UK
    Hum Mol Genet 12:3359-67. 2003
    ..disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are ..
  12. pmc Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice
    M A Hickey
    Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine, Reed Neurological Research Center B114, 710 Westwood Plaza, Los Angeles, CA 90095, USA
    Neuroscience 157:280-95. 2008
    Huntington's disease is a neurodegenerative disorder, caused by an elongation of CAG repeats in the huntingtin gene...
  13. ncbi Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse
    V C Wheeler
    Molecular Neurogenetics Unit, Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, USA
    Hum Mol Genet 8:115-22. 1999
    ..A similar pattern was obtained when this repeat was inserted into exon 1 of the mouse Hdh gene...
  14. pmc Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo
    B R Leavitt
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Am J Hum Genet 68:313-24. 2001
    ..yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 or YAC72) human huntingtin (htt), in a developmental- and tissue-specific manner, that is identical to endogenous htt...
  15. doi Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits
    Sofia Hult
    Translational Neuroendocrine Research Unit, Department of Experimental Medical Sciences, Lund University, Lund, Sweden
    Cell Metab 13:428-39. 2011
    In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed...
  16. doi Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis
    Juliette D Godin
    Institut Curie, Orsay F 91405, France
    Neuron 67:392-406. 2010
    b>Huntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis...
  17. ncbi Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse
    S J Tabrizi
    University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK
    Ann Neurol 47:80-6. 2000
    ..by an abnormally expanded (>36) CAG repeat within the ITI5 gene encoding a widely expressed 349-kd protein, huntingtin. The medium spiny neurons of the caudate preferentially degenerate in Huntington's disease, with the presence of ..
  18. ncbi Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice
    Alejandro Lloret
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Hum Mol Genet 15:2015-24. 2006
    ..instability of the HD CAG repeat and the striatal-specific somatic HD CAG repeat expansion, nuclear mutant huntingtin accumulation and intranuclear inclusion formation...
  19. ncbi Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus
    Juliette Gafni
    The Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA
    J Biol Chem 279:20211-20. 2004
    ..HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) tract expansion near the N terminus of huntingtin (Htt)...
  20. ncbi Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin
    Yuji Tanaka
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 21:381-91. 2006
    ..disorder characterized behaviorally by chorea, incoordination, and shortened lifespan and neuropathologically by huntingtin inclusions and neuronal degeneration...
  21. ncbi Body weight is modulated by levels of full-length huntingtin
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Hum Mol Genet 15:1513-23. 2006
    ..is an adult-onset neurodegenerative disorder that is caused by the expansion of a polyglutamine tract within the Huntingtin (htt) protein. Wild-type htt has been shown to be involved in transcription, transport and cell survival...
  22. pmc Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models
    Jack Phan
    Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095, USA
    Hum Mol Genet 18:1006-16. 2009
    ..gene expression and lipid accumulation in adipocytes can be recapitulated by expression of an inducible mutant huntingtin transgene in an adipocyte cell line and that mutant huntingtin inhibits transcriptional activity of the PGC-..
  23. ncbi Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin
    G Schilling
    Department of Psychiatry, Division of Neuropathology, Johns Hopkins University, Baltimore, MD 21205 2196, USA
    Hum Mol Genet 8:397-407. 1999
    ..an inherited, neurodegenerative disorder caused by the expansion of a glutamine repeat in the N-terminus of the huntingtin protein...
  24. ncbi Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease?
    L Kennedy
    Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, UK
    Hum Mol Genet 9:2539-44. 2000
    ..unstable CAG triplet repeat expansion encoding a polyglutamine stretch within the ubiquitously expressed protein huntingtin is responsible for causing Huntington's disease (HD)...
  25. ncbi Selective extra-dimensional set shifting deficit in a knock-in mouse model of Huntington's disease
    S P Brooks
    Cardiff University, Schools of Biological Sciences, Museum Avenue, PO Box 911, Cardiff CF10 3US, Wales, UK
    Brain Res Bull 69:452-7. 2006
    ..The aim of the present paper then, was to test whether homozygous knock-in mice derived from the Hdh(CAG(150)) mouse line were impaired in any of five 2-choice discrimination tasks (simple, compound, compound ..
  26. ncbi Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration
    Libin Cui
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129 USA
    Cell 127:59-69. 2006
    Huntington's disease (HD) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HD pathogenesis...
  27. ncbi Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage
    Alexandre Kuhn
    Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Hum Mol Genet 16:1845-61. 2007
    To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of ..
  28. pmc A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease
    Maria Björkqvist
    Neuronal Survival Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, S 221 00 Lund, Sweden
    J Exp Med 205:1869-77. 2008
    ..Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a ..
  29. pmc Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice
    Xiaofeng Gu
    Center for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA
    Neuron 64:828-40. 2009
    The N-terminal 17 amino acids of huntingtin (NT17) can be phosphorylated on serines 13 and 16; however, the significance of these modifications in Huntington's disease pathogenesis remains unknown...
  30. pmc In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington's disease subjects
    Mathilde Faideau
    CEA, Institute of Biomedical Imaging, Molecular Imaging Research Center, F 92265 Fontenay aux Roses, France
    Hum Mol Genet 19:3053-67. 2010
    ..disorder previously thought to be of primary neuronal origin, despite ubiquitous expression of mutant huntingtin (mHtt). We tested the hypothesis that mHtt expressed in astrocytes may contribute to the pathogenesis of HD...
  31. pmc Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z 4H4, BC, Canada
    BMC Neurosci 7:80. 2006
    Huntington disease (HD) is an adult onset neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin (htt) protein...
  32. ncbi Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype
    J G Hodgson
    Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Hum Mol Genet 5:1875-85. 1996
    ..The HD protein (huntingtin) plays a critical role in early embryonic development since homozygous targeted disruption of the murine HD gene ..
  33. ncbi Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene
    H Ishiguro
    Institute for Comprehensive Medical Science, Fujita Health University, Toyoake Aichi 470 1192, Japan
    J Neurosci Res 65:289-97. 2001
    ..Chimeric proteins composed of human mutated exon 1 and mouse huntingtin are expressed ubiquitously in brain and peripheral tissues...
  34. ncbi Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice
    I Dragatsis
    Department of Genetics and Development, Columbia University, New York, New York, USA
    Nat Genet 26:300-6. 2000
    ..On the basis of these results, we propose that huntingtin is required for neuronal function and survival in the brain and that a loss-of-function mechanism may contribute ..
  35. ncbi Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release
    Yeun Su Choo
    Department of Psychiatry, University of Alabama at Birmingham, 35294, USA
    Hum Mol Genet 13:1407-20. 2004
    Huntington's disease (HD) is initiated by an abnormally expanded polyglutamine stretch in the huntingtin protein, conferring a novel property on the protein that leads to the loss of striatal neurons...
  36. ncbi Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse models
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 21:444-55. 2006
    ..Neuropathological changes include the appearance of N-terminal huntingtin fragments, decreased brain weight and apoptotic neuronal loss in a select subset of neurons located in the ..
  37. pmc Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver
    Jong Min Lee
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS ONE 6:e23647. 2011
    Age at onset of Huntington's disease (HD) is largely determined by the CAG trinucleotide repeat length in the HTT gene...
  38. ncbi Targeted inactivation of the mouse Huntington's disease gene homolog Hdh
    M E MacDonald
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
    Cold Spring Harb Symp Quant Biol 61:627-38. 1996
  39. ncbi Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice
    Silvia Gines
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th St, Charlestown, MA 02129, USA
    Hum Mol Genet 12:497-508. 2003
    ..We found that reduced CRE-signaling in Hdh(Q111) striatum, monitored by brain derived neurotrophic factor and phospho-CRE binding protein (CREB), predated ..
  40. ncbi Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicity
    Ali Khoshnan
    Biology Division, California Institute of Technology, Pasadena, California 91125, USA
    J Neurosci 24:7999-8008. 2004
    Transcriptional dysregulation by mutant huntingtin (Htt) protein has been implicated in the pathogenesis of Huntington's disease (HD)...
  41. ncbi Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease
    Caroline L Benn
    King s College London, Medical and Molecular Genetics, GKT School of Medicine, UK
    Hum Mol Genet 14:3065-78. 2005
    In postmortem Huntington's disease brains, mutant htt is present in both nuclear and cytoplasmic compartments...
  42. pmc N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking
    Adam L Orr
    Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 28:2783-92. 2008
    Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the cytoplasm...
  43. pmc Impaired TrkB-mediated ERK1/2 activation in huntington disease knock-in striatal cells involves reduced p52/p46 Shc expression
    Silvia Gines
    Departament de Biologia Cel lular, Facultat de Medicina, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Casanova 143, E 08036 Barcelona, Spain
    J Biol Chem 285:21537-48. 2010
    ..Altered BDNF-mediated ERK1/2 activation in mutant huntingtin cells is associated with reduced expression of p52/p46 Shc docking proteins...
  44. ncbi The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtin
    W Auerbach
    Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Hum Mol Genet 10:2515-23. 2001
    b>Huntingtin is an essential protein that with mutant polyglutamine tracts initiates dominant striatal neurodegeneration in Huntington's disease (HD)...
  45. ncbi Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1
    Mamoru Shibata
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:14474-85. 2006
    Intracellular accumulation of mutant Huntingtin with expanded polyglutamine provides a context-dependent cytotoxicity critical for the pathogenesis of Huntington disease (Everett, C. M., and Wood, N. W. (2004) Brain 127, 2385-2405)...
  46. doi In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of Huntington disease
    Mary Y Heng
    Neuroscience Graduate Program and Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Neurosci 29:3200-5. 2009
    ..Our results are consistent with previous suggestions that direct and/or indirect interactions of mutant huntingtin with NMDARs are a proximate cause of neurodegeneration in HD.
  47. ncbi Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues
    I Dragatsis
    Department of Genetics, Columbia University, New York, NY 10032, USA
    Development 125:1529-39. 1998
    ..nullizygous for a targeted disruption of the Huntington's disease gene homologue (Hdh), which encodes a protein (huntingtin) of unknown biochemical function, become developmentally retarded and disorganized, and die early in development...
  48. ncbi HAP1-huntingtin interactions do not contribute to the molecular pathology in Huntington's disease transgenic mice
    F Bertaux
    Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, UK
    FEBS Lett 426:229-32. 1998
    HAP1 (huntingtin associated protein) has previously been found to interact with huntingtin (htt) in a glutamine length dependent manner and has been proposed to play a role in the cell specific neurodegeneration observed in Huntington's ..
  49. ncbi Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes
    M S Hurlbert
    Department of Medicine, University of Colorado Health Sciences Center, Denver, USA
    Diabetes 48:649-51. 1999
    ..syndrome of Huntington's disease has been modeled in transgenic mice by the expression of a portion of the human huntingtin gene together with 140 CAG repeats (the R6/2 strain)...
  50. ncbi Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease
    A Yamamoto
    Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
    Cell 101:57-66. 2000
    ..We have created a conditional model of HD by using the tet-regulatable system. Mice expressing a mutated huntingtin fragment demonstrate neuronal inclusions, characteristic neuropathology, and progressive motor dysfunction...
  51. pmc Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2
    Edoardo Marcora
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309, USA
    Proc Natl Acad Sci U S A 100:9578-83. 2003
    ..By using a yeast two-hybrid screen, we identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2), both of which are known to interact with ..
  52. pmc Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro
    Eugenia Trushina
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo ClinicFoundation, Rochester, Minnesota 55905, USA
    Mol Cell Biol 24:8195-209. 2004
    Recent data in invertebrates demonstrated that huntingtin (htt) is essential for fast axonal trafficking. Here, we provide direct and functional evidence that htt is involved in fast axonal trafficking in mammals...
  53. ncbi Polyglutamine expansion of huntingtin impairs its nuclear export
    Jonathan Cornett
    Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
    Nat Genet 37:198-204. 2005
    ..The mechanism by which mutant huntingtin (htt) accumulates intranuclearly is not known; wild-type htt, a 350-kDa protein of unknown function, is normally ..
  54. ncbi Age-dependent changes in the calcium sensitivity of striatal mitochondria in mouse models of Huntington's Disease
    N Brustovetsky
    Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Neurochem 93:1361-70. 2005
    Striatal and cortical mitochondria from knock-in and transgenic mutant huntingtin mice were examined for their sensitivity to calcium induction of the permeability transition, a cause of mitochondrial depolarization and ATP loss...
  55. ncbi Deletion of the triplet repeat encoding polyglutamine within the mouse Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo and elevated levels of ATP with cellular senescence in vitro
    Erin B D Clabough
    Department of Neuroscience, University of Virginia School of Medicine, PO Box 801392, 409 Lane Road, Charlottesville, VA 22908 1392, USA
    Hum Mol Genet 15:607-23. 2006
    b>Huntingtin (htt), the protein encoded by the Huntington's disease (HD) gene, contains a polymorphic stretch of glutamines (polyQ) near its N-terminus. When the polyQ stretch is expanded beyond 37Q, HD results...
  56. ncbi Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration
    Patrick Weydt
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA
    Cell Metab 4:349-62. 2006
    ..disease (HD) is a fatal, dominantly inherited disorder caused by polyglutamine repeat expansion in the huntingtin (htt) gene...
  57. pmc Huntingtin inhibits caspase-3 activation
    Yu Zhang
    Neuroapoptosis Laboratory, Department of Neurosurgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    EMBO J 25:5896-906. 2006
    Huntington's disease results from a mutation in the HD gene encoding for the protein huntingtin. The function of huntingtin, although beginning to be elucidated, remains largely unclear...
  58. pmc Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin
    Chuan En Wang
    Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Cell Biol 181:803-16. 2008
    Mutant huntingtin accumulates in the neuronal nuclei and processes, which suggests that its subcellular localization is critical for the pathology of Huntington's disease (HD)...
  59. doi Weight loss in Huntington disease increases with higher CAG repeat number
    N A Aziz
    Leiden University Medical Center, Department of Neurology, Leiden, The Netherlands
    Neurology 71:1506-13. 2008
    ..disease (HD) is a hereditary neurodegenerative disorder caused by an expanded number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown...
  60. pmc Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity
    Yoko Nekooki-Machida
    Tanaka Research Unit, RIKEN Brain Science Institute, Hirosawa 2 1, Wako, Saitama 351 0198, Japan
    Proc Natl Acad Sci U S A 106:9679-84. 2009
    ..Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under ..
  61. ncbi Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue
    S Zeitlin
    Department of Pathology, Columbia University, New York, New York 10032, USA
    Nat Genet 11:155-63. 1995
    The expansion of CAG triplet repeats in the translated region of the human HD gene, encoding a protein (huntingtin) of unknown function, is a dominant mutation leading to manifestation of Huntington's disease...
  62. ncbi Inactivation of the mouse Huntington's disease gene homolog Hdh
    M P Duyao
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
    Science 269:407-10. 1995
    ..disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function...
  63. ncbi Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes
    J Nasir
    Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Cell 81:811-23. 1995
    ..To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8...
  64. ncbi Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion
    J K White
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
    Nat Genet 17:404-10. 1997
    ..neurodegenerative disorder caused by a CAG repeat expansion that lengthens a glutamine segment in the novel huntingtin protein...
  65. ncbi A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice
    P F Shelbourne
    Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
    Hum Mol Genet 8:763-74. 1999
    ..the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene...
  66. ncbi A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration
    J G Hodgson
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Neuron 23:181-92. 1999
    ..yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 and YAC72) huntingtin (htt) in a developmental and tissue-specific manner identical to that observed in Huntington's disease (HD)...
  67. ncbi Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice
    V C Wheeler
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mol Genet 9:503-13. 2000
    Huntington's disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons...
  68. ncbi Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease
    L Menalled
    Department of Neurology and Mental Retardation Center, University of California at Los Angeles School of Medicine, Los Angeles, California 90095, USA
    Exp Neurol 162:328-42. 2000
    ..It is caused by the presence of an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function...
  69. ncbi Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity
    N R Jana
    Laboratory for CAG Repeat Diseases, RIKEN Brain Science Institute, Hirosawa, Japan
    Hum Mol Genet 9:2009-18. 2000
    ..is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear ..
  70. ncbi Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles
    P Hilditch-Maguire
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
    Hum Mol Genet 9:2789-97. 2000
    ..Huntington's disease (HD), with its selective neuronal cell loss, is caused by an elongated glutamine tract in the huntingtin protein...
  71. ncbi Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation
    J N Fain
    Departments of Molecular Sciences and Anatomy and Neurobiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Hum Mol Genet 10:145-52. 2001
    ..These data suggest that the obesity observed at 8-9 weeks in R6/2 mice may stem from a defect in fat breakdown by adipocytes...
  72. ncbi Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease mice
    H Li
    Department of Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 21:8473-81. 2001
    ..Here we report that in mice expressing full-length mutant huntingtin and modeling early stages of HD, neuropil aggregates form preferentially in the LGP and SN...
  73. ncbi Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease
    M B Bogdanov
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY 10021, USA
    J Neurochem 79:1246-9. 2001
    ..Immunocytochemistry showed increased OH(8)dG staining in late stages of the illness. These results suggest that oxidative damage may play a role in the pathogenesis of neuronal degeneration in the R6/2 transgenic mouse model of HD...
  74. ncbi Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease
    Melinda M Zeron
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, 221 84, Lund, Sweden
    Neuron 33:849-60. 2002
    ..vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice...
  75. ncbi Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice
    Vanessa C Wheeler
    Molecular Neurogenetics Unit and Molecular Neuropathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mol Genet 11:633-40. 2002
    In Huntington's disease (HD), CAG repeats extend a glutamine tract in huntingtin to initiate the dominant loss of striatal neurons and chorea...
  76. ncbi Lessons from animal models of Huntington's disease
    David C Rubinsztein
    Dept of Medical Genetics, Cambridge Institute of Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Trends Genet 18:202-9. 2002
    ..are translated into an abnormally long polyglutamine tract close to the N-terminus of the HD gene product, huntingtin. Studies in mouse models and human suggest that the mutation is associated with a deleterious gain of function...
  77. ncbi Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice
    Gabriele Schilling
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 13:1599-610. 2004
    Huntington's disease (HD) results from the expansion of a glutamine repeat near the N-terminus of huntingtin (htt)...
  78. ncbi Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules
    Laurent R Gauthier
    Unité Mixte de Recherche 146, Centre National de la Recherche Scientifique, Institut Curie, Building 110, Centre Universitaire, 91405 Orsay Cedex, France
    Cell 118:127-38. 2004
    Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and responsible for the neuronal toxicity associated with Huntington's disease (HD)...
  79. ncbi Biochemical, ultrastructural, and reversibility studies on huntingtin filaments isolated from mouse and human brain
    Miguel Diaz-Hernandez
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, 28029 Madrid, Spain
    J Neurosci 24:9361-71. 2004
    ..microscopy, both in human and mouse samples, revealed that the stable component of the inclusions are mutant huntingtin-containing and ubiquitin-containing fibrils...
  80. ncbi RNA association and nucleocytoplasmic shuttling by ataxin-1
    Stuart Irwin
    McMaster University, HSC 4H45, Department of Biochemistry, Hamilton, Ontario, L8N 3Z5, Canada
    J Cell Sci 118:233-42. 2005
    ..These results suggest that the normal role of ataxin-1 may be in RNA processing, perhaps nuclear RNA export. Thus, nuclear retention of mutant ataxin-1 may be an important toxic gain of function in SCA1 disease...
  81. ncbi Neuronal intranuclear inclusions and neuropil aggregates in HdhCAG(150) knockin mice
    S J Tallaksen-Greene
    Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
    Neuroscience 131:843-52. 2005
    ..Diffuse nuclear localization of huntingtin protein (htt) was noted initially within striatal neurons at approximately 28 weeks, followed by the development ..
  82. ncbi Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada
    J Neurosci 25:4169-80. 2005
    ....
  83. ncbi Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin
    Tamara Milakovic
    Department of Psychiatry, University of Alabama at Birmingham, Birmingham, Alabama 35294 0017, USA
    J Biol Chem 280:30773-82. 2005
    ..Nonetheless, the specific mitochondrial defects due to the presence of mutant huntingtin have not been fully elucidated...
  84. pmc Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Proc Natl Acad Sci U S A 102:11402-7. 2005
    We have serendipitously established a mouse that expresses an N-terminal human huntingtin (htt) fragment with an expanded polyglutamine repeat (approximately 120) under the control of the endogenous human promoter (shortstop)...
  85. ncbi Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brain
    Silvia Gines
    Departament de Biologia Cel lular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Casanova 143, E 08036 Barcelona, Spain
    Eur J Neurosci 23:649-58. 2006
    ..Our findings also demonstrated that continuous expression of mutant huntingtin is required to down-regulate TrkB levels...
  86. ncbi Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin
    Rona K Graham
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada
    Cell 125:1179-91. 2006
    Cleavage of huntingtin (htt) has been characterized in vitro, and accumulation of caspase cleavage fragments represents an early pathological change in brains of Huntington's disease (HD) patients...
  87. ncbi Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice
    Jorge M A Oliveira
    Buck Institute for Age Research, Novato, California, USA
    J Neurochem 101:241-9. 2007
    ..Moreover, moderate expression of full-length mutant huntingtin (in Hdh150 knock-in heterozygotes) does not significantly impair mitochondrial respiration in unstimulated ..
  88. pmc Huntingtin facilitates dynein/dynactin-mediated vesicle transport
    Juliane P Caviston
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 104:10045-50. 2007
    ..b>Huntingtin (Htt) is a vesicle-associated protein found in both neuronal and nonneuronal cells that is thought to be ..
  89. ncbi Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity
    Randy Singh Atwal
    Department of Biochemistry and Biomedical Sciences, McMaster University, HSC 4H24A, 1200 Main Street West, Hamilton, Ontario, Canada
    Hum Mol Genet 16:2600-15. 2007
    Huntington's disease is caused by an expanded polyglutamine tract in huntingtin protein, leading to accumulation of huntingtin in the nuclei of striatal neurons...
  90. pmc HAP1 can sequester a subset of TBP in cytoplasmic inclusions via specific interaction with the conserved TBP(CORE)
    Justin R Prigge
    Veterinary Molecular Biology, Molecular Biosciences, Montana State University, 960 Technology Blvd, Bozeman, MT 59717, USA
    BMC Mol Biol 8:76. 2007
    ..atrophy, and spinocerebellar ataxia 17 (SCA17) are caused by expansions in the polyglutamine (polyQ) repeats in Huntingtin protein (Htt), androgen receptor protein (AR), and TATA-binding protein (TBP), respectively...
  91. pmc Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load
    Austen J Milnerwood
    Deptartment of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada
    J Physiol 585:817-31. 2007
    ..Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD...
  92. pmc Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor
    Tomoyuki Yamanaka
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan
    EMBO J 27:827-39. 2008
    In Huntington's disease (HD), mutant Huntingtin, which contains expanded polyglutamine stretches, forms nuclear aggregates in neurons...
  93. pmc DNA instability in postmitotic neurons
    Roman Gonitel
    Department of Medical and Molecular Genetics, King s College London School of Medicine, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 105:3467-72. 2008
    ....
  94. doi Time course of choice reaction time deficits in the Hdh(Q92) knock-in mouse model of Huntington's disease in the operant serial implicit learning task (SILT)
    Rebecca C Trueman
    School of Biosciences, Cardiff University, Cardiff, Wales, UK
    Behav Brain Res 189:317-24. 2008
    ..We have previously reported that knock-in Hdh(Q92/Q92) mice exhibit a modest impairment in learning the SILT tasks at 4 months of age, prior to the formation of ..
  95. pmc Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons
    Emilie Colin
    Institut Curie, Orsay, France
    EMBO J 27:2124-34. 2008
    ..However, the mechanisms that determine the directionality of transport remain unclear. Huntingtin, the protein mutated in Huntington's disease, is a positive regulatory factor for vesicular transport...
  96. doi Polyglutamine-modulated striatal calpain activity in YAC transgenic huntington disease mouse model: impact on NMDA receptor function and toxicity
    Catherine M Cowan
    Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurosci 28:12725-35. 2008
    Huntington disease (HD), caused by CAG expansion in the ubiquitously expressed huntingtin gene, is characterized by early dysfunction and death of striatal medium-sized spiny neurons (MSNs)...
  97. doi Enhanced sensitivity of striatal neurons to axonal transport defects induced by mutant huntingtin
    Lu Shiun Her
    Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Neurosci 28:13662-72. 2008
    ..HD) is an autosomal dominant neurodegenerative disease linked to a polyQ (polyglutamine) expansion in the huntingtin protein...
  98. pmc Acetylation targets mutant huntingtin to autophagosomes for degradation
    Hyunkyung Jeong
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129, USA
    Cell 137:60-72. 2009
    ..disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in ..
  99. pmc IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin
    Ali Khoshnan
    Biology Division 216 76, California Institute of Technology, Pasadena, California, USA
    PLoS ONE 4:e5768. 2009
    Proteolysis of huntingtin (Htt) plays a key role in the pathogenesis of Huntington's disease (HD). However, the environmental cues and signaling pathways that regulate Htt proteolysis are poorly understood...
  100. pmc Alterations in cortical excitation and inhibition in genetic mouse models of Huntington's disease
    Damian M Cummings
    Mental Retardation Research Center, David Geffen School of Medicine, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA 90095, USA
    J Neurosci 29:10371-86. 2009
    ..Furthermore, the differences between synaptic phenotypes in cortex and striatum are important for the development of future therapeutic approaches, which may need to be targeted early in the development of the phenotype...
  101. pmc Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicity
    Charity T Aiken
    Department of Developmental and Cell Biology, University of California, Irvine, California 92697, USA
    J Biol Chem 284:29427-36. 2009
    b>Huntingtin (Htt) is a widely expressed protein that causes tissue-specific degeneration when mutated to contain an expanded polyglutamine (poly(Q)) domain...

Research Grants14

  1. Does cortex kill striatum in HD?
    CHRISTOPHER MEADE; Fiscal Year: 2004
    An important question in Huntington's disease (HD) pathogenesis is whether mutant huntingtin (Ht) effects striatal cell death directly by perturbing striatal cell fL motion or whether it alters areas outside the striatum (notably cortex) ..
  2. Neuroprotective Effects of Enhanced Proteasome Function
    BARBARA SNIDER; Fiscal Year: 2006
    ....
  3. Combination Drug Therapy in Huntington's Disease
    ROBERT FERRANTE; Fiscal Year: 2008
    ..neurological disorder caused by an expanded CAG repeat in the gene coding for a protein of unknown function, huntingtin (htt). There is no known treatment for HD...
  4. BIOPHYSICAL STUDY OF ANTIPSYCHOTICS BEHAVIORAL EFFECTS
    Stephen Fowler; Fiscal Year: 2009
    ..The results will improve our understanding of the pharmacological basis of dopamine related behaviors and assist in the discovery of improved antipsychotic medications. ..
  5. NMDA RECEPTOR DEVELOPMENT IN NEOSTRIATUM
    Michael Levine; Fiscal Year: 2001
    ..The outcomes will provide information necessary to understand the role of these receptors in NS development and provide clues for generating rational strategies to treat GluR dysfunction during development and in the adult. ..
  6. OXIDATIVE INJURY IN PARKINSONS DISEASE
    ROBERT FERRANTE; Fiscal Year: 2002
    ..These studies will have direct relevance to understanding the pathogenesis of PD and to developing new therapies. ..
  7. 2003 Gordon Conference on CAG Triplet Repeat Disorders
    Michael Levine; Fiscal Year: 2003
    ..All participants (except speakers and discussants) will be required to present posters. Priority will be given to women, minorities, and persons with disabilities when selecting participants. ..
  8. 2005 CAG Triplet Repeat Disorders Gordon Conference
    Michael Levine; Fiscal Year: 2005
    ..All participants will be required to present posters. Priority will be given to women, minorities, and persons with disabilities when selecting participants. ..
  9. Modulation of ataxin-1 phosphorylation
    Harry Orr; Fiscal Year: 2006
    ..Lead compounds that have been validated will be used to begin preclinical testing using a mouse model of SCA1. ..
  10. Embryonic Stem Cell Model of Polyglutamine Disease
    MATTHEW LORINCZ; Fiscal Year: 2007
    ..The roles of the normal and mutant HD gene product, huntingtin remain uncertain...
  11. RECEPTOR GENE TRANSCRIPTION IN HUNTINGTON'S DISEASE
    Jang Ho Cha; Fiscal Year: 2008
    ..Specific Aim 1 will test the hypothesis that mutant huntingtin selectively alters the association of Sp1 with the promoters of genes that are downregulated in HD...
  12. Neurophysiological Modulation by Dopamine in the Neostriatum
    Michael Levine; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  13. Effects of estrogen on neuropathophysiology and behavior in Huntington's disease
    JENELLE DORNER; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  14. Neuropathology and Pathogenesis of Huntington's Disease
    Anton Reiner; Fiscal Year: 2008
    ..While the mutated huntingtin protein (Htt) that underlies HD pathogenesis appears to interfere with a wide array of cellular functions, the ..