huntington disease

Summary

Summary: A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)

Top Publications

  1. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004
  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. pmc Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression
    Dongbo Yu
    Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Cell 150:895-908. 2012
  4. ncbi Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain
    M Difiglia
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:1990-3. 1997
  5. ncbi Molecular mechanisms and potential therapeutical targets in Huntington's disease
    Chiara Zuccato
    Department of Pharmacological Sciences and Centre for Stem Cell Research, Universita degli Studi di Milano, Milan, Italy
    Physiol Rev 90:905-81. 2010
  6. ncbi Huntington's disease: from molecular pathogenesis to clinical treatment
    Christopher A Ross
    Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Lancet Neurol 10:83-98. 2011
  7. pmc A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing
    Eulalia Marti
    Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation CRG, Catalonia, Spain
    Nucleic Acids Res 38:7219-35. 2010
  8. pmc Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis
    Holly B Kordasiewicz
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Neuron 74:1031-44. 2012
  9. pmc Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease
    Kirupa Sathasivam
    Department of Medical and Molecular Genetics, King s College London, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 110:2366-70. 2013
  10. 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

Detail Information

Publications278 found, 100 shown here

  1. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004
    b>Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates...
  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. pmc Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression
    Dongbo Yu
    Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Cell 150:895-908. 2012
    Mutant huntingtin (HTT) protein causes Huntington disease (HD), an incurable neurological disorder. Silencing mutant HTT using nucleic acids would eliminate the root cause of HD...
  4. ncbi Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain
    M Difiglia
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:1990-3. 1997
    ..Ubiquitin was also found in NIIs and DNs, which suggests that abnormal huntingtin is targeted for proteolysis but is resistant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD...
  5. ncbi Molecular mechanisms and potential therapeutical targets in Huntington's disease
    Chiara Zuccato
    Department of Pharmacological Sciences and Centre for Stem Cell Research, Universita degli Studi di Milano, Milan, Italy
    Physiol Rev 90:905-81. 2010
    ....
  6. ncbi Huntington's disease: from molecular pathogenesis to clinical treatment
    Christopher A Ross
    Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Lancet Neurol 10:83-98. 2011
    ..Thus, Huntington's disease is also emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset...
  7. pmc A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing
    Eulalia Marti
    Genetic Causes of Disease Group, Genes and Disease Program, Centre for Genomic Regulation CRG, Catalonia, Spain
    Nucleic Acids Res 38:7219-35. 2010
    b>Huntington disease (HD) is a neurodegenerative disorder that predominantly affects neurons of the forebrain...
  8. pmc Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis
    Holly B Kordasiewicz
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Neuron 74:1031-44. 2012
    ..Rather than requiring continuous treatment, our findings establish a therapeutic strategy for sustained HD disease reversal produced by transient ASO-mediated diminution of huntingtin synthesis...
  9. pmc Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease
    Kirupa Sathasivam
    Department of Medical and Molecular Genetics, King s College London, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 110:2366-70. 2013
    b>Huntington disease (HD) is a devastating, late-onset, inherited neurodegenerative disorder that manifests with personality changes, movement disorders, and cognitive decline...
  10. 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
    ..These studies suggest a key role for PGC-1alpha in the control of energy metabolism in the early stages of HD pathogenesis...
  11. pmc Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice
    Michelle Gray
    Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 28:6182-95. 2008
    ..In summary, the BACHD model constitutes a novel and robust in vivo paradigm for the investigation of HD pathogenesis and treatment...
  12. 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
    ..These findings are consistent with the idea that N-terminal fragments of huntingtin with a repeat expansion are toxic to neurons, and that N-terminal fragments are prone to form both intranuclear inclusions and neuritic aggregates...
  13. 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
    ..The appearance in transgenic mice of these inclusions, followed by characteristic morphological change within neuronal nuclei, is strikingly similar to nuclear abnormalities observed in biopsy material from HD patients...
  14. ncbi Huntington's disease
    Francis O Walker
    Department of Neurology, Wake Forest University, Medical Center Blvd, Winston Salem, NC 27157, USA
    Lancet 369:218-28. 2007
    ..The precise pathophysiological mechanisms of Huntington's disease are poorly understood, but research in transgenic animal models of the disorder is providing insight into causative factors and potential treatments...
  15. ncbi Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
    J S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, California 92697, USA
    Nature 413:739-43. 2001
    ..These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms...
  16. ncbi Regional and progressive thinning of the cortical ribbon in Huntington's disease
    H D Rosas
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 02129 4404, USA
    Neurology 58:695-701. 2002
    ....
  17. pmc SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease
    Michal Mielcarek
    Department of Medical and Molecular Genetics, King s College London, London, United Kingdom
    PLoS ONE 6:e27746. 2011
    ..We found that SAHA reduces SDS-insoluble aggregate load in the cortex and brain stem but not in the hippocampus of the R6/2 brains, and that this was accompanied by restoration of Bdnf cortical transcript levels...
  18. pmc Neurocognitive signs in prodromal Huntington disease
    Julie C Stout
    School of Psychology, Psychiatry, and Psychological Medicine, Monash University, UT, USA
    Neuropsychology 25:1-14. 2011
    PREDICT-HD is a large-scale international study of people with the Huntington disease (HD) CAG-repeat expansion who are not yet diagnosed with HD...
  19. ncbi Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: analysis of 24 month observational data
    Sarah J Tabrizi
    UCL Institute of Neurology, University College London, Queen Square, London, UK
    Lancet Neurol 11:42-53. 2012
    ..TRACK-HD is a prospective observational biomarker study in premanifest and early Huntington's disease (HD). In this report we define a battery of potential outcome measures for therapeutic trials...
  20. ncbi Glutamine repeats and neurodegeneration
    H Y Zoghbi
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Annu Rev Neurosci 23:217-47. 2000
    ..this review, we summarize the clinicopathologic features of these disorders (spinobulbar muscular atrophy, Huntington disease, and the spinocerebellar ataxias, including dentatorubropallidoluysian atrophy), describe the genes involved ..
  21. pmc Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease
    Marta Martinez-Vicente
    Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Neurosci 13:567-76. 2010
    ..We propose that inefficient engulfment of cytosolic components by autophagosomes is responsible for their slower turnover, functional decay and accumulation inside HD cells...
  22. ncbi Altered microRNA regulation in Huntington's disease models
    Soon Tae Lee
    Neurodegeneration Research Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    Exp Neurol 227:172-9. 2011
    ..Our results show that transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD...
  23. ncbi Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease
    C Zuccato
    Department of Pharmacological Sciences, University of Milano, Via Balzaretti 9, 20133 Milano, Italy
    Science 293:493-8. 2001
    ..This leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD...
  24. ncbi Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis
    Sarah J Tabrizi
    UCL Institute of Neurology, University College London, Department of Neurodegenerative Disease, Queen Square, London, UK
    Lancet Neurol 10:31-42. 2011
    ..We report 12-month longitudinal changes, building on baseline findings...
  25. pmc Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
    Emma Hockly
    Medical and Molecular Genetics, Guy s, King s and St Thomas School of Medicine, King s College London, Eighth Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 100:2041-6. 2003
    ..SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics...
  26. pmc Tracking mutant huntingtin aggregation kinetics in cells reveals three major populations that include an invariant oligomer pool
    Maya A Olshina
    Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, Victoria 3010, Australia
    J Biol Chem 285:21807-16. 2010
    b>Huntington disease is caused by expanded polyglutamine sequences in huntingtin, which procures its aggregation into intracellular inclusion bodies (IBs)...
  27. pmc SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis
    Ruth Luthi-Carter
    Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
    Proc Natl Acad Sci U S A 107:7927-32. 2010
    ..Furthermore, the ascertainment of SIRT2's role in regulating cellular metabolism demonstrates a central function shared with other sirtuin proteins...
  28. ncbi Trinucleotide repeat disorders
    Harry T Orr
    Institute of Human Genetics, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Annu Rev Neurosci 30:575-621. 2007
    ..disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy...
  29. ncbi Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation
    Jim P Dompierre
    Institut Curie and Centre National de la Recherche Scientifique Unité Mixte de Recherche 146, Orsay, France
    J Neurosci 27:3571-83. 2007
    ..Our findings reveal that HDAC6 inhibition and acetylation at lysine 40 of alpha-tubulin may be therapeutic targets of interest in disorders such as HD in which intracellular transport is altered...
  30. pmc OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells
    Irina V Kovtun
    Department of Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA
    Nature 447:447-52. 2007
    ..Age-dependent CAG expansion provides a direct molecular link between oxidative damage and toxicity in post-mitotic neurons through a DNA damage response, and error-prone repair of single-strand breaks...
  31. ncbi Huntingtin-protein interactions and the pathogenesis of Huntington's disease
    Shi Hua Li
    Department of Human Genetics, Emory University, School of Medicine, Atlanta, GA 30322, USA
    Trends Genet 20:146-54. 2004
    ..In this article, we focus on the potential roles of huntingtin-protein interactions in the pathogenesis of Huntington's disease...
  32. 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
    ....
  33. 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
    b>Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein...
  34. pmc Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection"
    H Diana Rosas
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    Neuroimage 49:2995-3004. 2010
    ..Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing...
  35. ncbi Development of biomarkers for Huntington's disease
    David W Weir
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
    Lancet Neurol 10:573-90. 2011
    ..Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease...
  36. pmc ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease
    Pamela Maher
    Department of Cellular Neurobiology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Hum Mol Genet 20:261-70. 2011
    ..Thus, fisetin, resveratrol and related compounds might be useful for the treatment of HD by virtue of their unique ability to activate ERK...
  37. ncbi Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
    Montserrat Arrasate
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94141, USA
    Nature 431:805-10. 2004
    ..Surprisingly, inclusion body formation predicts improved survival and leads to decreased levels of mutant huntingtin elsewhere in a neuron. Thus, inclusion body formation can function as a coping response to toxic mutant huntingtin...
  38. 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
    ....
  39. pmc Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice
    Ryan L Boudreau
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52240, USA
    Mol Ther 17:1053-63. 2009
    ..Together, these encouraging and surprising findings support further testing of nonallele-specific RNAi therapeutics for HD...
  40. pmc Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data
    Sarah J Tabrizi
    UCL Institute of Neurology, University College London, Queen Square, London, UK
    Lancet Neurol 8:791-801. 2009
    ..Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated HTT and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions...
  41. pmc Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin
    Jeffrey B Carroll
    Program in Neuroscience, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Mol Ther 19:2178-85. 2011
    b>Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT)...
  42. ncbi SUMO modification of Huntingtin and Huntington's disease pathology
    Joan S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, CA 92697, USA
    Science 304:100-4. 2004
    ..Lysine mutations that prevent both SUMOylation and ubiquitination of Httex1p reduce HD pathology, indicating that the contribution of SUMOylation to HD pathology extends beyond preventing Htt ubiquitination and degradation...
  43. 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
    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)...
  44. pmc Quantitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into huntington's disease molecular pathogenesis
    Jason Miller
    Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA
    J Neurosci 30:10541-50. 2010
    ..Finally, the model that emerges from our quantitative measurements places critical limits on the potential mechanisms by which mutant htt might induce neurodegeneration, which should help direct future research...
  45. ncbi Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity
    F C Nucifora
    Division of Neurobiology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Science 291:2423-8. 2001
    ..Thus, polyglutamine-mediated interference with CBP-regulated gene transcription may constitute a genetic gain of function, underlying the pathogenesis of polyglutamine disorders...
  46. 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
    ..Because of their early behavioral anomalies and regionally specific pathology, these mice provide a powerful tool with which to evaluate the effectiveness of new therapies and to study the mechanisms involved in the neuropathology of HD...
  47. ncbi Trinucleotide repeat length instability and age of onset in Huntington's disease
    M Duyao
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129
    Nat Genet 4:387-92. 1993
    ..The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis...
  48. 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
    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...
  49. pmc The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease
    Amy N Packer
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurosci 28:14341-6. 2008
    ..These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates...
  50. ncbi Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice
    Austen J Milnerwood
    Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
    Neuron 65:178-90. 2010
    ..We provide a candidate mechanism linking several pathways previously implicated in HD pathogenesis and demonstrate successful early therapeutic intervention in mice...
  51. ncbi Role of brain-derived neurotrophic factor in Huntington's disease
    Chiara Zuccato
    Department of Pharmacological Sciences and Centre for Stem Cell Research, University of Milano, Via Balzaretti 9, 20133 Milan, Italy
    Prog Neurobiol 81:294-330. 2007
    ....
  52. ncbi Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease
    Gabriella Gardian
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York 10021, USA
    J Biol Chem 280:556-63. 2005
    ....
  53. ncbi Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Hum Mol Genet 12:1555-67. 2003
    An expanded CAG repeat is the underlying genetic defect in Huntington disease, a disorder characterized by motor, psychiatric and cognitive deficits and striatal atrophy associated with neuronal loss...
  54. ncbi The detection and measurement of locomotor deficits in a transgenic mouse model of Huntington's disease are task- and protocol-dependent: influence of non-motor factors on locomotor function
    Patrick N Pallier
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom
    Brain Res Bull 78:347-55. 2009
    ....
  55. ncbi Mechanisms of neurodegeneration in Huntington's disease
    Joana M Gil
    Island Medical Program, Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
    Eur J Neurosci 27:2803-20. 2008
    ..This review presents an overview of the mechanisms that may contribute for HD pathogenesis. Ultimately, a better understanding of these mechanisms will lead to the development of more effective therapeutic targets...
  56. pmc Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease
    Maria Filimonenko
    Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
    J Cell Biol 179:485-500. 2007
    ..Together, our data indicate that efficient autophagic degradation requires functional MVBs and provide a possible explanation to the observed neurodegenerative phenotype seen in patients with CHMP2B mutations...
  57. pmc Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients
    Edith L Pfister
    Department of Medicine, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Curr Biol 19:774-8. 2009
    ..We have designed and validated selective siRNAs for the three SNP sites, laying the foundation for allele-specific RNA interference (RNAi) therapy for HD...
  58. pmc Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington's disease: zQ175
    Liliana B Menalled
    PsychoGenics Inc, Tarrytown, New York, United States of America
    PLoS ONE 7:e49838. 2012
    ..These data suggest that the zQ175 knock-in line could be a suitable model for the evaluation of therapeutic approaches and early events in the pathogenesis of HD...
  59. 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
    ..Together, our findings demonstrate that serines 13 and 16 are critical determinants of fl-mhtt-induced disease pathogenesis in vivo, supporting the targeting of huntingtin NT17 domain and its modifications in HD therapy...
  60. pmc Characterization of neurophysiological and behavioral changes, MRI brain volumetry and 1H MRS in zQ175 knock-in mouse model of Huntington's disease
    Taneli Heikkinen
    Charles River Discovery Research Services, Kuopio, Finland
    PLoS ONE 7:e50717. 2012
    ....
  61. ncbi TR-FRET-based duplex immunoassay reveals an inverse correlation of soluble and aggregated mutant huntingtin in huntington's disease
    Barbara Baldo
    Neuroscience Discovery, Novartis Institutes for BioMedical Research, Basel CH 4002, Switzerland
    Chem Biol 19:264-75. 2012
    ..These results emphasize the assay's efficiency for highly sensitive and quantitative detection of soluble and aggregated mHtt and its application in high-throughput screening and characterization of HD models...
  62. ncbi The progression of regional atrophy in premanifest and early Huntington's disease: a longitudinal voxel-based morphometry study
    Nicola Z Hobbs
    Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK
    J Neurol Neurosurg Psychiatry 81:756-63. 2010
    ..They may also provide tools for assessing disease-modifying interventions. The authors investigated the progression of regional atrophy in premanifest and early HD compared with controls...
  63. pmc Antioxidants in Huntington's disease
    Ashu Johri
    Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10065, USA
    Biochim Biophys Acta 1822:664-74. 2012
    ..This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease...
  64. pmc The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at CAG/CTG repeats
    Agathi Vasiliki Goula
    Department of Neurogenetics and Translational Medicine, Institute of Genetics and Molecular and Cellular Biology IGBMC, UMR 7104 CNRS INSERM UdS, Illkirch, France
    Biochemistry 51:3919-32. 2012
    ..Our results show that the BER stoichiometry, nucleotide sequence, and DNA damage position modulate repair outcome and suggest that a suboptimal long-patch BER activity promotes CAG/CTG repeat instability...
  65. 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
    ..These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia...
  66. pmc Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease
    Guy Keryer
    Institut Curie, Orsay, France
    J Clin Invest 121:4372-82. 2011
    b>Huntington disease (HD) is a devastating autosomal-dominant neurodegenerative disorder...
  67. pmc CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches
    Douglas R Langbehn
    Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 1000, USA
    Am J Med Genet B Neuropsychiatr Genet 153:397-408. 2010
    ..The Langbehn et al. model appears accurate enough to have substantial utility in various research contexts. We also emphasize remaining caveats, many of which are relevant for any direct application to genetic counseling...
  68. 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
    ..This supports the continued use of the more high-throughput fragment models to identify mechanisms of pathogenesis and for preclinical screening...
  69. pmc Exendin-4 improves glycemic control, ameliorates brain and pancreatic pathologies, and extends survival in a mouse model of Huntington's disease
    Bronwen Martin
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland, USA
    Diabetes 58:318-28. 2009
    ..Similarly to Huntington's disease patients, mice expressing the mutated human huntingtin protein also exhibit neurodegenerative changes, motor dysfunction, perturbed energy metabolism, and elevated blood glucose levels...
  70. pmc Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease
    Kirupa Sathasivam
    Department of Medical and Molecular Genetics, King s College London School of Medicine, King s College London, 8th Floor Tower Wing, Guy s Tower, Great Maze Pond, London, UK
    Hum Mol Genet 19:65-78. 2010
    ....
  71. ncbi Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA
    Yu Lai Wang
    Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry NCNP, Tokyo 187 8502, Japan
    Neurosci Res 53:241-9. 2005
    ..Treatments using this siRNA significantly prolonged model mice longevity, improved motor function and slowed down the loss of body weight. This work suggests that siRNA-based therapy is promising as a future treatment for HD...
  72. ncbi A microRNA-based gene dysregulation pathway in Huntington's disease
    Rory Johnson
    Genome Institute of Singapore, 60 Biopolis Street, 02 01 Genome, Singapore 138672, Singapore
    Neurobiol Dis 29:438-45. 2008
    ....
  73. ncbi A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference
    Maria Stella Lombardi
    Medtronic Bakken Research Center, Corporate Science and Technology, 6229 GW Maastricht, The Netherlands
    Exp Neurol 217:312-9. 2009
    ..reduce huntingtin protein (htt) expression in affected brain regions may provide an effective treatment for Huntington disease (HD), but it remains uncertain whether suppression of both wild-type and mutant alleles in a heterozygous ..
  74. pmc Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's disease
    Caroline L Benn
    Department of Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London, UK
    PLoS ONE 4:e5747. 2009
    ..Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7...
  75. pmc Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease
    Rodrigo A Quintanilla
    Department of Anesthesiology, University of Rochester, University Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    J Biol Chem 283:25628-37. 2008
    ..potential neuroprotective role of PPARgamma activation in preventing the loss of mitochondrial function in Huntington disease (HD)...
  76. ncbi The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease
    S E Andrew
    Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Nat Genet 4:398-403. 1993
    ..Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent for affected parent-child pairs...
  77. pmc Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits
    M Difiglia
    Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02114, USA
    Proc Natl Acad Sci U S A 104:17204-9. 2007
    ....
  78. 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
    ....
  79. ncbi Normal huntingtin function: an alternative approach to Huntington's disease
    Elena Cattaneo
    Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milano, Italy
    Nat Rev Neurosci 6:919-30. 2005
    ....
  80. ncbi Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice
    G J Klapstein
    Mental Retardation Research Center, University of California, Los Angeles, California 90095, USA
    J Neurophysiol 86:2667-77. 2001
    ..These physiological and morphological alterations will affect communication in the basal ganglia circuitry. Furthermore, they suggest areas to target for pharmacotherapies to alleviate and reduce the symptoms of HD...
  81. ncbi Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington's disease transgenic mice
    Edward C Stack
    Geriatric Research Education and Clinical Center, Bedford Veterans Administration Medical Center, Bedford, Massachusetts 01730, USA
    J Comp Neurol 490:354-70. 2005
    ....
  82. pmc Increased susceptibility of cytoplasmic over nuclear polyglutamine aggregates to autophagic degradation
    Atsushi Iwata
    Department of Biological Sciences, Bio X Program, Stanford University, Stanford, CA 94305 5430
    Proc Natl Acad Sci U S A 102:13135-40. 2005
    ..These data indicate that autophagy is a critical component of the cellular clearance of toxic protein aggregates and may help to explain why protein aggregates are more toxic when directed to the nucleus...
  83. ncbi Global changes to the ubiquitin system in Huntington's disease
    Eric J Bennett
    Department of Biological Sciences, Stanford University, Stanford, California 94305, USA
    Nature 448:704-8. 2007
    ..Thus, HD is linked to global changes in the ubiquitin system to a much greater extent than previously recognized...
  84. ncbi Marked differences in neurochemistry and aggregates despite similar behavioural and neuropathological features of Huntington disease in the full-length BACHD and YAC128 mice
    Mahmoud A Pouladi
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, and Child and Family Research Institute, Vancouver, BC, Canada
    Hum Mol Genet 21:2219-32. 2012
    The development of animal models of Huntington disease (HD) has enabled studies that help define the molecular aberrations underlying the disease...
  85. pmc CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion
    J M Lee
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
    Neurology 78:690-5. 2012
    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat...
  86. pmc Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease
    John Labbadia
    Department of Medical and Molecular Genetics, King s College London, London, UK
    J Clin Invest 121:3306-19. 2011
    b>Huntington disease (HD) is a devastating neurodegenerative disorder for which there are no disease-modifying treatments...
  87. pmc Allele-selective inhibition of huntingtin expression by switching to an miRNA-like RNAi mechanism
    Jiaxin Hu
    The Departments of Pharmacology and Biochemistry, UT Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390 9041, USA
    Chem Biol 17:1183-8. 2010
    ..Potent, allele selective inhibition of HTT by mismatched RNAs provides a new option for developing HD therapeutics...
  88. ncbi Sustained effects of nonallele-specific Huntingtin silencing
    Valérie Drouet
    Commissariat a l Energie Atomique, Institute of Biomedical Imaging I2BM and Molecular Imaging Research Center, France
    Ann Neurol 65:276-85. 2009
    ..But whether an allele-specific silencing of mutant htt or a nonallele-specific silencing should be considered has not been addressed...
  89. 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
    ..These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration...
  90. 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
    ....
  91. ncbi Early synaptic pathophysiology in neurodegeneration: insights from Huntington's disease
    Austen J Milnerwood
    Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, Canada
    Trends Neurosci 33:513-23. 2010
    ..Further understanding the primary effects of gene mutations associated with late-onset neurodegeneration should translate to novel treatments for HD families and guide therapeutic strategies for other neurodegenerative diseases...
  92. pmc Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity
    H Diana Rosas
    Center for Neuro imaging of Aging and Neurodegenerative Diseases, 149 13th Street Room 2275, Charlestown, MA 02129, USA
    Brain 131:1057-68. 2008
    ....
  93. pmc Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice
    Agathi Vassiliki Goula
    Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology, UMR 7104 CNRS INSERM UdS, Illkirch, France
    PLoS Genet 5:e1000749. 2009
    ..We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion...
  94. ncbi In vivo evidence for the selective subcortical degeneration in Huntington's disease
    Gwenaelle Douaud
    URA CEA CNRS 2210, SHFJ, Orsay, France
    Neuroimage 46:958-66. 2009
    ....
  95. 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
    ..These mice will serve as useful reagents in experiments designed to reveal the molecular nature of neuronal dysfunction underlying HD...
  96. 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 thus demonstrate that a continuous influx of the mutant protein is required to maintain inclusions and symptoms, raising the possibility that HD may be reversible...
  97. pmc A fully humanized transgenic mouse model of Huntington disease
    Amber L Southwell
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 22:18-34. 2013
    Silencing the mutant huntingtin gene (muHTT) is a direct and simple therapeutic strategy for the treatment of Huntington disease (HD) in principle...
  98. pmc Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease
    John P Miller
    Buck Institute for Age Research, Novato, CA 94945, USA
    Neuron 67:199-212. 2010
    ..Correspondingly, MMPs are activated in HD mouse models, and loss of function of Drosophila homologs of MMPs suppresses Htt-induced neuronal dysfunction in vivo...
  99. pmc A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model
    Andrey S Tsvetkov
    Gladstone Institute of Neurological Disease and Taube Koret Center for Huntington s Disease Research and Consortium for Fronto temporal Dementia Research, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 107:16982-7. 2010
    ..special relevance for neurodegenerative proteinopathies, such as Alzheimer disease, Parkinson disease, and Huntington disease (HD), which are characterized by the accumulation of misfolded proteins...
  100. pmc Differential vulnerability of neurons in Huntington's disease: the role of cell type-specific features
    Ina Han
    Department of Anatomy and Cell Biology University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Neurochem 113:1073-91. 2010
    ....

Research Grants65

  1. MEMBRANE FUSION ATPASES AND THE GOLGI APPARATUS
    Ayano Satoh; Fiscal Year: 2007
    ..protein aggregates has implicated this ATPase in neurodegenerative diseases ranging from Alzheimer's to Huntington disease. Insights into the molecular mechanism of Golgi reassembly may therefore provide insight into these medical ..
  2. Human embryonic stem cell-derived neural crest stem cells and Hirschsprung disea
    Sean J Morrison; Fiscal Year: 2010
    ..Trials</keyword;keyword>Epilepsy/therapy</keyword;keyword>Humans</keyword;keyword>Huntington Disease/therapy</keyword;keyword>Neurons/*transplantation</keyword;keyword>Parkinson Disease/therapy</..
  3. MALDI-TOF/TOF MS TO SUPPORT BIOMEDICAL RESEARCH
    Catherine E Costello; Fiscal Year: 2012
    ..Disease, Alzheimer Disease, familial and sporadic systemic amyloid diseases, prion diseases, Cancer, Huntington Disease, Lyme and Rheumatoid Arthritis, Sickle Cell Disease, Traumatic Brain Injury, infectious diseases and ..
  4. NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS
    Solomon H Snyder; Fiscal Year: 2013
    ..health includes the possibility that drugs inhibiting Rhes-mutant huntingtin binding will delay/prevent Huntington Disease brain damage...
  5. RNAi therapy for Huntingtons disease: safety & efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2010
    ..Testing the utility of RNA interference in a nonhuman primate model of HD is a necessary and key step towards its potential use in the clinic. ..
  6. MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY
    THOMAS ALEXANDER COOPER; Fiscal Year: 2013
    ..disorders such as Spinocerebellar Ataxia 8 (SCA8), Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), and Huntington Disease-Like 2 (HDL2)...
  7. Mitochondrial Porin in Bioenergetic Defects in Huntingtons Disease
    Nickolay Brustovetsky; Fiscal Year: 2013
    ....
  8. DEVELOPING PET AGENTS FOR IMAGING PHOSPHODIESTERASE 10A (PDE10A)
    Zhude Tu; Fiscal Year: 2012
    ..A PET radiotracer of PDE10A may help physician to quantify the progression of Huntington Disease based on the PET measurement of PDE10A level in patients with the Huntington disease patients.
  9. RNAi therapy for Huntingtons disease: safety &efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2013
    ..The studies proposed here, along with the didactic and applied training, will be invaluable in assisting my transition from a post-doctoral fellow to an independent investigator. ..
  10. Validation of the HD-HRQOL (Huntington disease quality of life measure)
    Noelle E Carlozzi; Fiscal Year: 2013
    ..More recently, the NINDS has extended these measurement development efforts to include Huntington disease (HD)-a fatal, insidious, progressive neurodegenerative disease characterized by abnormalities in motor, ..
  11. Signaling Pathways Regulating Neuronal Survival
    SANTOSH R D'MELLO; Fiscal Year: 2013
    ..to using paradigms of neuronal death unrelated to disease states, we will study the role of HDAC3 in Huntington disease (HD) pathogenesis...
  12. PGC-1alpha and GABAergic Dysfunction in Huntington Disease
    Rita Marie Cowell; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Huntington Disease (HD) is a devastating neurological disorder that occurs in as many as 7 in every 100,000 people...
  13. Quantitative evaluation of 3D mouse behaviors in the open field using markerless
    D Michele Basso; Fiscal Year: 2012
    ..The result would be an automated method that produces accurate, sensitive, repeatable measurements of open-field movements for use in quantitative evaluations of motor performance. ..
  14. Synaptic processing in the basal ganglia
    David J Perkel; Fiscal Year: 2012
    ..because a variety of disorders such as autism spectrum disorder, schizophrenia, Parkinson disease and Huntington disease involve the basal ganglia, this research also has the potential to have long- term impact on those disorders...
  15. Gene-environment interactions between manganese exposure and Huntington disease
    Aaron B Bowman; Fiscal Year: 2012
    ..Finally, by exploring a gene-environment interface that moderates the onset and progression of HD, this study seeks to reveal mechanistic detail for how convergent genetic and environmental factors can enhance or suppress disease. ..
  16. Pathophysiology of dystonia: animal models
    Ellen J Hess; Fiscal Year: 2010
    ..Unlike Parkinson disease or Huntington disease where cell death provides clues to the pathogenesis of the movement disorder, dystonia is a functional ..
  17. Mechanisms for chromatin modification during transcription elongation
    Bing Li; Fiscal Year: 2013
    ..Importantly, human Set2 has been shown to interact with Huntingtin, the Huntington disease protein;and the treatment of histone deacetylase inhibitors can arrest neurodegeneration in a model system...
  18. Preclinical neuroprotective trials of a PPAR-gamma agonist in HD mouse models
    Wenzhen Duan; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Huntington disease (HD) is a neurodegenerative disease that is caused by the pathological elongation of the CAG repeats in the huntingtin gene...
  19. Molecular Mechanism of Imac-dependent axonal transport
    STEPHEN RAIKER; Fiscal Year: 2013
    ..of molecular motors has been implicated the neurodegenerative disorders: Amyotrophic Lateral Sclerosis, Huntington disease and Parkinson's disease...
  20. Modulation of the PPAR-delta Signaling Pathway in Huntingtons Disease
    Audrey S Dickey; Fiscal Year: 2013
    ..By elucidating the role of the PPAR [unreadable] signaling pathway in HD, targets for treatment may be found not only for HD, but other polyglutamine diseases and neurodegenerative diseases. ..
  21. Molecular Mechanisms of Endocytosis
    Andrew J Bean; Fiscal Year: 2010
    ..A better appreciation of the mechanism of endocytic protein sorting will help in understanding learning and memory and diseases in which protein transport is disturbed like cancer, lysosomal storage disorders, and Huntingtons Disease. ..
  22. Instability of Triplet Repeats in Mammalian Cells
    John H Wilson; Fiscal Year: 2013
    ..Expansions of CAG repeats in specific human genes cause numerous neurological diseases, including Huntington disease, myotonic dystrophy, and several spinocerebellar ataxias...
  23. Age of Onset and Huntingtons Disease
    CYNTHIA THERESE MCMURRAY; Fiscal Year: 2010
    ..In a reverse approach, we will reduce biomarker production in HD150KI mice by treatment with anti-oxidants, and test whether somatic expansion is also reduced. ..
  24. SNRP Program at UCC
    Maria Bykhovskaia; Fiscal Year: 2012
    ..Three new scientists will address the issues of oxidative damage in Huntington disease, direct effects of thyroid hormones on the nAChR and on synapse remodelling, and modulation of potassium ..
  25. DEVELOPING A MOUSE RETINAL MODEL OF NEURODEGENERATIVE DISEASE
    Marc I Diamond; Fiscal Year: 2012
    ..We are carrying out proof-of-concept experiments using the huntingtin (Htt) protein, which causes Huntington disease when it contains an elongated tract of glutamines...
  26. SUMOylation and Amyloid-beta elevation
    Ottavio Arancio; Fiscal Year: 2013
    ..has been implicated in the pathogenesis of several neurodegenerative disorders, including Parkinson disease, Huntington disease, and AD, but its role in AD remains to be clarified...
  27. Targeted Synaptic Proteomics
    Junmin Peng; Fiscal Year: 2012
    ..tested to profile PSD components in a cellular model of synaptic activation and during the development of Huntington disease. The study will establish an SRM-based strategy for targeted quantitative PSD analysis...
  28. Energy Balance and Neurodegenerative Disease
    Robert G Kalb; Fiscal Year: 2013
    ..Several mouse models of Amyotrophic Lateral Sclerosis (ALS) and Huntington Disease display a hypermetabolic phenotype - there is excessive resting energy expenditure...
  29. 2013 Parkinson's Study Group Symposium
    Michael A Schwarzschild; Fiscal Year: 2013
    ..and peer-reviewed platform and poster presentations on movement disorders including Parkinson disease, Huntington disease, Dystonia, Ataxia, and Tremor...
  30. A gene and prgenitor cell therapy in Huntington disease mice
    Anthony Wing Sang Chan; Fiscal Year: 2013
    ..To achieve our goals, we have two specific aims: (1) Determine neuronal differentiation properties of genetically modulated rHD-NPCs and (2) Determine the efficacy of rHD-NPC-siHD2 graft in rescuing the abnormal phenotype of HD mice. ..
  31. RNA mediated Neurotoxicity in Huntington's Disease-Like 2 and Huntington Disease
    DOBRILA DODA RUDNICKI; Fiscal Year: 2013
    ..abstract_text> ..
  32. Mechanism of gate-opening in the 20S proteasome induced by the proteasomal ATPase
    Yifan Cheng; Fiscal Year: 2012
    ..g. Huntington disease. The eukaryotic 26S proteasome is formed by a 20S proteasome with the proteolytic active sites sequestered ..
  33. POLYGLUTAMINE NEUROTOXICITY IN SBMA
    Diane E Merry; Fiscal Year: 2010
    ..characterized by protein misfolding and accumulation;these diseases include Alzheimer's disease, Huntington disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS)...
  34. Functional Connectivity in Premanifest Huntington's Disease
    STEPHEN MARK RAO; Fiscal Year: 2013
    ..provided by applicant): Brain mechanisms underlying subtle cognitive changes in the premanifest stage of Huntington disease (prHD) are not understood due to a relative dearth of functional imaging studies...
  35. Neuroimaging Analysis Center (NAC)
    Ron Kikinis; Fiscal Year: 2013
    ..traumatic encephalopathy, methamphetamine addiction and AIDS, schizophrenia, Alzheimer's disease, Huntington disease, autism, and image guided therapy...
  36. Identification of Biomarkers of Huntington Disease in Human and Rat
    Yvette Bordelon; Fiscal Year: 2012
    ..b>Huntington disease (HD), is an ideal disorder to carry out these objectives as the mutation has been identified, animal models ..
  37. Nuclear toxicity of Huntington disease protein
    Xiao Jiang Li; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Huntington disease (HD) is the most common form of polyglutamine diseases that are featured by abnormal gene expression caused ..
  38. A Next Generation of Biomarkers for Incipient Huntington Disease
    Clemens R Scherzer; Fiscal Year: 2013
    ..If confirmed, this next generation of biomarkers will transform clinical trial design and will enable earlier and more effective intervention. ..
  39. Genetic Testing for Huntington Disease in At Risk Adolescents and Young Adults
    KIMBERLY ANDREA QUAID; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Huntington Disease (HD) is a late onset neuropsychiatric disorder that is inherited in an autosomal dominant manner meaning that each child of an affected parent has a 50% chance of inheriting the ..
  40. Derivation of Functional Neurons from Human Adult Cells by Nonviral Gene Delivery
    Kam W Leong; Fiscal Year: 2013
    ..making them an attractive cell source for cell-based therapy of CNS disorders such as epilepsy, stroke, Huntington disease, and Parkinson's disease...
  41. Neuronal function of huntingtin associated protein
    Xiao Jiang Li; Fiscal Year: 2013
    ..Huntingtin-associated protein-1 (Hap1) was first identified as a cytoplasmic protein that interacts with the Huntington disease protein huntingtin...
  42. Synaptic toxicity of Huntington disease protein
    Xiao Jiang Li; Fiscal Year: 2013
    ..These studies also have implications for our understanding of synaptic dysfunction in other age-dependent neurodegenerative diseases that are also caused by misfolded proteins. ..
  43. Basal Ganglia Shape Analysis and Circuitry in Huntington's Disease
    Christopher A Ross; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Huntington disease (HD) is a progressive, fatal, neurodegenerative disease, with movement disorder, psychiatric features, and cognitive decline...
  44. Coenzyme Q10 in Huntingtons Disease
    Merit E Cudkowicz; Fiscal Year: 2013
    ..Secondary measures include changes in the other clinical rating scales of the Unified Huntington Disease Rating Scale, time to decline in TFC by 2 and 3 points, ability to complete the study at the assigned ..
  45. Validation of ubiquilin for Huntingtons disease
    Mervyn J Monteiro; Fiscal Year: 2013
    ..We describe the next logical steps of how this could be done. ..
  46. Coordination and Statistics for Coenzyme Q10 in Huntington's Disease
    Michael P McDermott; Fiscal Year: 2013
    ..Secondary measures include changes in the other clinical rating scales of the Unified Huntington Disease Rating Scale, time to decline in TFC by 2 and 3 points, ability to complete the study at the assigned ..
  47. Genetic modifiers of Predict-HD phenotypes
    James F Gusella; Fiscal Year: 2013
    ..SNP data for more than 6,000 HD individuals from the Huntington Study Group COHORT study, the European Huntington Disease Network's Registry study and a collection of banked post-mortem HD brains...
  48. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2007
    ..mediators (19,20), and delays disease progression in animal models of neurodegenerative disorders, including Huntington disease (19), Parkinson disease (21) and ALS (22) (Serge Przedborski, personal communication)...
  49. Celestrols for Treatment of Neurodegenerative Diseases
    Richard Silverman; Fiscal Year: 2007
    ..by our laboratory and others who participated recently in a screening program organized by the NINDS, Huntington Disease Society of America, Hereditary Disease Foundation, and the ALSA to identify new drugs for treating these ..
  50. NR2B Mediated Neurotoxicity in Murine Huntington Disease Model
    Roger L Albin; Fiscal Year: 2013
    ..Summary/Abstract Objectives: Our objective is to delineate proximate mechanisms of neurodegeneration in Huntington disease (HD), an uncommon, adult-onset, autosomal neurodegenerative disorder...
  51. Calcium channels as novel therapeutic targets for Huntingtons Disease
    ILYA B BEZPROZVANNY; Fiscal Year: 2013
    ..Validation of CaV1.3 VGCC and TRPC1 SOC channels as novel therapeutic targets for HD will create an opportunity for developing novel therapeutic agents for cure of HD. ..
  52. HUNTINGTON DISEASE IN VENEZUELA AND OTHER STUDIES
    Nancy Wexler; Fiscal Year: 2001
    ..8) To explore how psychiatric and cognitive symptomatology can also be regulated by the expanded repeat or some other genetic modifiers. 9) To characterize the kind-red for common disorders and genetic traits or markers. ..
  53. Glycolipid Replacement Therapy for Huntingtons Disease
    Shawn DeFrees; Fiscal Year: 2012
    ..We have developed novel potent, orally bioavailable analogs of GM1 which can solve this road-block and become the first disease modifying treatment for HD. ..
  54. NEUROPATHOLOGY AND PATHOGENESIS OF HUNTINGTON' DISEASE
    Anton Reiner; Fiscal Year: 2004
    ....
  55. HIGH RESOLUTION PHYSICAL MAPS OF 4P AND 5Q
    JOHN WASMUTH; Fiscal Year: 1992
    ..In addition to answering specific questions about these two regions of the human genome, the approaches to be developed and used in this project should aid in mapping other portions of the genome...
  56. NGF GRAFTS AND HUNTINGTONS DISEASE
    Jeffrey Kordower; Fiscal Year: 2000
    ..It is proposed that these studies will determine the breadth of protection afforded by trophic-factor secreting transplants and elucidate the mechanisms by which the protection can occur. ..
  57. Integrated approach to protein biomarker identification in Huntington Disease
    Sushmita Roy; Fiscal Year: 2013
    ..provided by applicant): This project proposes the mining of plasma and cerebrospinal fluid (CSF) biomarkers of disease progression in Huntington Disease (HD) using the latest analytical tools to accelerate future treatment studies.
  58. MUTATIONS INDUCED IN HUMAN SPERM BY CANCER THERAPY
    Marvin Meistrich; Fiscal Year: 1999
    ..and CEB1 loci and at the microsatellite trinucleotide repeats associated with the myotonic dystrophy and Huntington disease loci and the androgen receptor gene...
  59. METHODS FOR CLONING THE HUNTINGTONS DISEASE GENE
    Leon Carlock; Fiscal Year: 1993
    ..In either case, extending these studies to the entire HD gene region should allow the identification of this elusive gene...
  60. CHROMOSOME MAPPING BY A DNA CIRCULARIZATION TECHNIQUE
    Francis Collins; Fiscal Year: 1992
    ..The application of jumping techniques to Huntington disease, cystic fibrosis, the major histocompatibility complex of man, and neurofibromatosis will be continued, in ..
  61. TRANSGLUTAMINASE AND DISEASES OF EXPANDED POLYGLUTAMINE
    Howard Green; Fiscal Year: 2002
    DESCRIPTION (adapted from applicant's abstract): Huntington disease and eight other central nervous system diseases are each caused by a protein containing an expanded sequence of polyglutamine...
  62. National Research Roster of Huntington Disease Patients and Families
    Tatiana Foroud; Fiscal Year: 2009
    ..the continued maintenance and expansion of the National Research Roster of patients and families affected by Huntington Disease. The Contractor shall collect data on persons with Huntington Disease, persons at risk of the Disease, and ..
  63. FUNCTIONAL BRAIN IMAGING AND MENTAL DISORDERS IN AGING
    Gary Small; Fiscal Year: 1999
    ..The goals of the proposed study parallel our successful ongoing studies of Huntington disease. We will identify presymptomatic putative FAD gene carriers, determine the time course for cerebral ..
  64. World Congress of Huntington's Disease 2009
    Jane Paulsen; Fiscal Year: 2009
    This R13 conference grant is to provide support for the World Congress on Huntington Disease (WCHD). The WCHD 2009 will take place September 13th through September 15th in Vancouver, British Columbia in Canada...
  65. HUNTINGTON DISEASE: A NEUROLOGICAL MARKER OF AGING
    JOE CHRISTIAN; Fiscal Year: 1993
    b>Huntington disease (HD) is an autosomal dominant disease characterized by premature central nervous system degeneration, primarily in the striatum of medium-sized spiney neurons. HD has a relentless 15-20 year course from onset to death...