huntingtin

Summary

Gene Symbol: huntingtin
Description: huntingtin
Alias: IT15, LOMARS, huntingtin, huntington disease protein
Species: human

Top Publications

  1. 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
  2. ncbi Mitogen- and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death
    Emmanuel Roze
    Universite Pierre et Marie Curie Paris 6, CNRS, UMR 7102, 9 Quai St Bernard, 75005, Paris, France
    FASEB J 22:1083-93. 2008
  3. pmc Proteomic analysis of wild-type and mutant huntingtin-associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis
    Brady P Culver
    Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 287:21599-614. 2012
  4. pmc The huntingtin N17 domain is a multifunctional CRM1 and Ran-dependent nuclear and cilial export signal
    T Maiuri
    Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON, Canada
    Hum Mol Genet 22:1383-94. 2013
  5. pmc Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues
    Meewhi Kim
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    Prion 7:221-8. 2013
  6. doi The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease
    Jiří Klempíř
    Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
    Mov Disord 26:125-9. 2011
  7. pmc Identification of a karyopherin β1/β2 proline-tyrosine nuclear localization signal in huntingtin protein
    Carly R Desmond
    Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N3Z5
    J Biol Chem 287:39626-33. 2012
  8. pmc Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity
    Wenjun Song
    Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA
    Nat Med 17:377-82. 2011
  9. ncbi Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi
    Francois G Gervais
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada H9R 4P8
    Nat Cell Biol 4:95-105. 2002
  10. ncbi Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme
    M A Kalchman
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4
    J Biol Chem 271:19385-94. 1996

Research Grants

  1. Blocking Huntingtin Toxicity by Intrabody
    Xiao Jiang Li; Fiscal Year: 2006
  2. Developmental effects of 5-HTT genotype on stress reactivity and brain function
    Moriah E Thomason; Fiscal Year: 2010
  3. David R Corey; Fiscal Year: 2016
  4. Elaine L Bearer; Fiscal Year: 2016
  5. Nelly Alia-Klein; Fiscal Year: 2014
  6. Solomon H Snyder; Fiscal Year: 2016
  7. RNAi therapy for Huntingtons disease: safety & efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2010
  8. Nickolay Brustovetsky; Fiscal Year: 2015
  9. RNAi therapy for Huntingtons disease: safety &efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2013
  10. SANTOSH R D'MELLO; Fiscal Year: 2016

Detail Information

Publications295 found, 100 shown here

  1. 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)...
  2. ncbi Mitogen- and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death
    Emmanuel Roze
    Universite Pierre et Marie Curie Paris 6, CNRS, UMR 7102, 9 Quai St Bernard, 75005, Paris, France
    FASEB J 22:1083-93. 2008
    ..HD) is a neurodegenerative disorder due to an abnormal polyglutamine expansion in the N-terminal region of huntingtin protein (Exp-Htt). This expansion causes protein aggregation and neuronal dysfunction and death...
  3. pmc Proteomic analysis of wild-type and mutant huntingtin-associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis
    Brady P Culver
    Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 287:21599-614. 2012
    Huntington disease is a neurodegenerative disorder caused by a CAG repeat amplification in the gene huntingtin (HTT) that is reflected by a polyglutamine expansion in the Htt protein...
  4. pmc The huntingtin N17 domain is a multifunctional CRM1 and Ran-dependent nuclear and cilial export signal
    T Maiuri
    Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON, Canada
    Hum Mol Genet 22:1383-94. 2013
    The first 17 amino acids of Huntington's disease (HD) protein, huntingtin, comprise an amphipathic alpha-helical domain that can target huntingtin to the endoplasmic reticulum (ER)...
  5. pmc Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues
    Meewhi Kim
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    Prion 7:221-8. 2013
    ..neurodegenerative disorder caused by a polyglutamine (polyQ) expansion (> 35Q) in the first exon (EX1) of huntingtin protein (Htt)...
  6. doi The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease
    Jiří Klempíř
    Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
    Mov Disord 26:125-9. 2011
    ..3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and ..
  7. pmc Identification of a karyopherin β1/β2 proline-tyrosine nuclear localization signal in huntingtin protein
    Carly R Desmond
    Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N3Z5
    J Biol Chem 287:39626-33. 2012
    ..b>Huntingtin, a 350-kDa protein, has defined roles in the nucleus, as well as a CRM1/exportin-dependent nuclear export signal;..
  8. pmc Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity
    Wenjun Song
    Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA
    Nat Med 17:377-82. 2011
    ..an inherited and incurable neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in huntingtin (encoded by HTT)...
  9. ncbi Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi
    Francois G Gervais
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada H9R 4P8
    Nat Cell Biol 4:95-105. 2002
    In Huntington disease, polyglutamine expansion of the protein huntingtin (Htt) leads to selective neurodegenerative loss of medium spiny neurons throughout the striatum by an unknown apoptotic mechanism...
  10. ncbi Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme
    M A Kalchman
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4
    J Biol Chem 271:19385-94. 1996
    ..enzyme (hE2-25K) as a protein that interacts with the gene product for Huntington disease (HD) (Huntingtin)...
  11. pmc Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease
    Nan Wang
    1 Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA 2 Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA 3
    Nat Med 20:536-41. 2014
    ..neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal ..
  12. pmc Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease
    Juliette D Godin
    Institut Curie, Orsay, France
    EMBO J 29:2433-45. 2010
    ..We report here a new pathological mechanism by which mutant huntingtin specifically interferes with the degradation of beta-catenin...
  13. ncbi PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains
    Jan Modregger
    Institute for Biochemistry II, University of Cologne, D 50931 Cologne, Germany
    Hum Mol Genet 11:2547-58. 2002
    ..disease (HD) is caused by a pathological expansion of a CAG repeat in the first exon of the gene coding for huntingtin, resulting in an abnormally long polyglutamine stretch...
  14. pmc dAtaxin-2 mediates expanded Ataxin-1-induced neurodegeneration in a Drosophila model of SCA1
    Ismael Al-Ramahi
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS Genet 3:e234. 2007
    ..Altogether, these findings reveal a previously unknown functional link between neurodegenerative disorders with common clinical features but different etiology...
  15. 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
    ..However, our data suggest that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression...
  16. pmc Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism
    Jong Min Lee
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS Genet 3:e135. 2007
    The Huntington's disease (HD) CAG repeat, encoding a polymorphic glutamine tract in huntingtin, is inversely correlated with cellular energy level, with alleles over approximately 37 repeats leading to the loss of striatal neurons...
  17. pmc Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression
    Mahmoud A Pouladi
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, and Child and Family Research Institute, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 19:1528-38. 2010
    Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length...
  18. ncbi Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease
    Anthone W Dunah
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Center for Aging, Genetics and Neurodegeneration, Charlestown, MA 02129, USA
    Science 296:2238-43. 2002
    ..disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis...
  19. 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 ..
  20. doi Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments
    Simon C Warby
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z4H4, Canada
    Mol Cell Neurosci 40:121-7. 2009
    b>Huntingtin is phosphorylated on serine-421 (S421) by the pro-survival signaling protein kinases Akt and SGK...
  21. ncbi Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease
    E Hermel
    The Buck Institute for Age Research, Novato, CA, USA
    Cell Death Differ 11:424-38. 2004
    ..Proteolytic processing of full-length mutant huntingtin (Htt) and subsequent events may play an important role in the selective neuronal cell death found in this ..
  22. pmc Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity
    Ji Yeon Shin
    Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Cell Biol 171:1001-12. 2005
    ..However, little is known about the role of glia in HD neuropathology. Here, we report that mutant huntingtin accumulates in glial nuclei in HD brains and decreases the expression of glutamate transporters...
  23. 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)...
  24. ncbi Huntingtin contains a highly conserved nuclear export signal
    Jianrun Xia
    Department of Biochemistry, McMaster University, Health Sciences Centre Rm 4H45, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
    Hum Mol Genet 12:1393-403. 2003
    ..CAG DNA expansion results in a polyglutamine tract expansion in mutant huntingtin protein...
  25. 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...
  26. pmc Prevalence of incompletely penetrant Huntington's disease alleles among individuals with major depressive disorder
    Roy H Perlis
    Center for Human Genetic Research and the Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
    Am J Psychiatry 167:574-9. 2010
    Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington's disease may have higher levels of depressive symptoms than healthy comparison populations...
  27. 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)...
  28. ncbi Progressive and selective striatal degeneration in primary neuronal cultures using lentiviral vector coding for a mutant huntingtin fragment
    Diana Zala
    Institute of Neurosciences, Swiss Federal Institute of Technology Lausanne, EPFL, 1015 Lausanne, Switzerland
    Neurobiol Dis 20:785-98. 2005
    A lentiviral vector expressing a mutant huntingtin protein (htt171-82Q) was used to generate a chronic model of Huntington's disease (HD) in rat primary striatal cultures...
  29. ncbi HYPK, a Huntingtin interacting protein, reduces aggregates and apoptosis induced by N-terminal Huntingtin with 40 glutamines in Neuro2a cells and exhibits chaperone-like activity
    Swasti Raychaudhuri
    Structural Genomics Section, Saha Institute of Nuclear Physics, 1 AF Bidhan Nagar, Kolkata 700 064, India
    Hum Mol Genet 17:240-55. 2008
    Expansion of polymorphic glutamine (Q) numbers present at the protein Huntingtin (Htt) beyond 36Q results in its misfolding and aggregation, and the aggregates recruit several other proteins...
  30. pmc Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin
    Gerardo A Morfini
    Department of Anatomy and Cell Biology, University of Illinois at Chicago, USA
    Nat Neurosci 12:864-71. 2009
    ..These data identify JNK3 as a critical mediator of polyQ-Htt toxicity and provide a molecular basis for polyQ-Htt-induced inhibition of FAT...
  31. pmc Cdc42-interacting protein 4 binds to huntingtin: neuropathologic and biological evidence for a role in Huntington's disease
    Sebastien Holbert
    Laboratory of Genomic Biology, Institut National de la Santé et de la Recherche Médicale Avenir Group and Fondation Jean Dausset Centre d Etude du Polymorphisme Humain, 75010 Paris, France
    Proc Natl Acad Sci U S A 100:2712-7. 2003
    Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt)...
  32. ncbi Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin
    Hui Yang
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 W Lombard Street, Baltimore, MD 21201, USA
    Exp Cell Res 313:538-50. 2007
    ..We tested this idea by using polyglutamine (polyQ)-containing huntingtin (htt) protein as a model substrate...
  33. ncbi Huntingtin interacts with a family of WW domain proteins
    P W Faber
    Molecular Neurogenetics Unit, Massachusetts General Hospital East, Building 149, 13th Street, Charlestown, MA 02129, USA
    Hum Mol Genet 7:1463-74. 1998
    The hallmark neuropathology of Huntington's disease (HD) is due to elongation of a polyglutamine segment in huntingtin, a novel approximately 350 kDa protein of unknown function...
  34. ncbi Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease
    V O Ona
    Department of Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 399:263-7. 1999
    ..The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K)...
  35. pmc Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1
    Tie Shan Tang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Neuron 39:227-39. 2003
    Huntington's disease (HD) is caused by polyglutamine expansion (exp) in huntingtin (Htt)...
  36. ncbi Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form
    Y Trottier
    Institut de Genetique et de Biologie Moleculaire et Cellulaire IGBMC, CNRS, INSERM, ULP, Illkirch, France
    Nat Genet 10:104-10. 1995
    ..To study the HD gene product (huntingtin), we have developed monoclonal antibodies raised against four different regions of the protein...
  37. ncbi Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract
    Y P Goldberg
    Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    Nat Genet 13:442-9. 1996
    ..Here we show that apoptotic extracts and apopain itself specifically cleave the HD gene product, huntingtin. The rate of cleavage increases with the length of the huntingtin polyglutamine tract, providing an explanation ..
  38. ncbi Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract
    C L Wellington
    Centre for Molecular Medicine and Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
    J Biol Chem 273:9158-67. 1998
    ..We now report that, similar to huntingtin, atrophin-1, ataxin-3, and the androgen receptor are cleaved in apoptotic extracts...
  39. ncbi Amyloid formation by mutant huntingtin: threshold, progressivity and recruitment of normal polyglutamine proteins
    C C Huang
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
    Somat Cell Mol Genet 24:217-33. 1998
    ..by an expanded CAG trinucleotide repeat encoding a tract of consecutive glutamines near the amino terminus of huntingtin, a large protein of unknown function...
  40. ncbi Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation
    P F Behrens
    Department of Neurology, Universitatsklinik Freiburg, Germany
    Brain 125:1908-22. 2002
    ..alterations in brain glutamate handling we studied transgenic mice expressing an N-terminal fragment of mutant huntingtin (R6/2)...
  41. 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
    Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion...
  42. ncbi Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation
    Gregor Schaffar
    Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D 82152 Martinsried, Germany
    Mol Cell 15:95-105. 2004
    ..We show, in vitro and in cells, that monomers or small soluble oligomers of huntingtin exon1 accumulate in the nucleus and inhibit the function of TBP in a polyQ-dependent manner...
  43. ncbi cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues
    Ming Chang Chiang
    Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica and Institute of Neuroscience, National Yang Ming University, Taipei 11529, Taiwan
    J Biol Chem 280:14331-40. 2005
    ..disease is a neurodegenerative disease resulting from a CAG (glutamine) trinucleotide expansion in exon 1 of the Huntingtin (Htt) gene...
  44. ncbi Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics CMMT, British Columbia Children s and Women s Hospital, University of British Columbia, 980 West 28th Avenue, Vancouver, British Columbia V5Z 4H4, Canada
    Hum Mol Genet 14:1569-77. 2005
    Huntington disease (HD) results from polyglutamine expansion in the huntingtin protein (htt). Despite the widespread tissue expression pattern of htt, neuronal loss is highly selective to medium spiny neurons of the striatum...
  45. ncbi HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism
    Ihn Sik Seong
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Richard B Simches Research Center, Boston, MA 02114, USA
    Hum Mol Genet 14:2871-80. 2005
    The 'expanded' HD CAG repeat that causes Huntington's disease (HD) encodes a polyglutamine tract in huntingtin, which first targets the death of medium-sized spiny striatal neurons...
  46. ncbi Wild-type huntingtin protects neurons from excitotoxicity
    Blair R Leavitt
    Centre for Molecular Medicine and Therapeutics, British Colombia Research Institute for Children s and Women s Health, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurochem 96:1121-9. 2006
    b>Huntingtin is a caspase substrate, and loss of normal huntingtin function resulting from caspase-mediated proteolysis may play a role in the pathogenesis of Huntington disease...
  47. ncbi Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons
    Diane T W Chang
    Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Neurobiol Dis 22:388-400. 2006
    Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine repeat in the huntingtin gene (Htt). Mitochondrial defects and protein aggregates are characteristic of affected neurons...
  48. ncbi Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism
    Daniel del Toro
    Departament de Biologia Cel lular i Anatomia Patològica, Facultat de Medicina, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, 08036 Barcelona, Spain
    J Neurosci 26:12748-57. 2006
    ..In view of these data and the involvement of huntingtin in intracellular trafficking, we examined the intracellular transport and release of Val66Val BDNF (Val-BDNF) ..
  49. 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...
  50. ncbi R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice
    Anton Reiner
    Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    J Comp Neurol 505:603-29. 2007
    ..while cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein.
  51. pmc Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism
    Ashwani K Thakur
    Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA
    Nat Struct Mol Biol 16:380-9. 2009
    ..We show here that the 17-amino-acid flanking sequence (HTT(NT)) N-terminal to the polyQ in the toxic huntingtin exon 1 fragment imparts onto this peptide a complex alternative aggregation mechanism...
  52. 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
    ..It is caused by expansion of a CAG repeat in the first exon of the huntingtin (HTT) gene that encodes a mutant HTT protein with a polyglutamine (polyQ) expansion at the amino terminus...
  53. pmc An N-terminal nuclear export signal regulates trafficking and aggregation of Huntingtin (Htt) protein exon 1
    Zhiqiang Zheng
    Department of Neurology, Washington University, St Louis, Missouri 63110, USA
    J Biol Chem 288:6063-71. 2013
    ..is a dominantly inherited neurodegenerative condition caused by polyglutamine expansion in the N terminus of the huntingtin protein (Htt). The first 17 amino acids (N17) of Htt play a key role in regulating its toxicity and aggregation...
  54. pmc TR-FRET assays of Huntingtin protein fragments reveal temperature and polyQ length-dependent conformational changes
    Xiaotian Cui
    1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China 2
    Sci Rep 4:5601. 2014
    ..One of the well established examples is the TR-FRET assay for mutant huntingtin protein (HTT), which is the major cause of the neurodegenerative Huntington's disease (HD)...
  55. ncbi Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins
    Kun Huang
    Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
    Neuron 44:977-86. 2004
    ..Here, using biochemical assays, we show that huntingtin (htt) interacting protein, HIP14, is a neuronal palmitoyl transferase (PAT)...
  56. ncbi Huntingtin associates with acidic phospholipids at the plasma membrane
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:36464-73. 2005
    We have identified a domain in the N terminus of huntingtin that binds to membranes...
  57. ncbi p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity
    Shouqing Luo
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Hum Mol Genet 17:895-905. 2008
    Huntington's disease (HD) is caused by a polyglutamine (polyQ) expansion in the huntingtin (htt) protein. While aggregation is a pathological hallmark of HD and related polyQ expansion diseases, the role of aggregates has been disputed...
  58. pmc Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity
    Xueyi Li
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Mol Cell Biol 29:6106-16. 2009
    b>Huntingtin (Htt) localizes to endosomes, but its role in the endocytic pathway is not established. Recently, we found that Htt is important for the activation of Rab11, a GTPase involved in endosomal recycling...
  59. pmc Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle
    Gregor P Lotz
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    J Biol Chem 285:38183-93. 2010
    Inclusion bodies of aggregated mutant huntingtin (htt) fragments are a neuropathological hallmark of Huntington disease (HD)...
  60. pmc A screen for enhancers of clearance identifies huntingtin as a heat shock protein 90 (Hsp90) client protein
    Barbara Baldo
    Neuroscience Pathway, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    J Biol Chem 287:1406-14. 2012
    Mechanisms to reduce the cellular levels of mutant huntingtin (mHtt) provide promising strategies for treating Huntington disease (HD)...
  61. pmc Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin
    Nicholas Stephane Caron
    Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5
    Proc Natl Acad Sci U S A 110:14610-5. 2013
    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG expansion within the huntingtin gene that encodes a polymorphic glutamine tract at the amino terminus of the huntingtin protein...
  62. pmc Expanded polyglutamine-containing N-terminal huntingtin fragments are entirely degraded by mammalian proteasomes
    Katrin Juenemann
    From the Department of Cellbiology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands and
    J Biol Chem 288:27068-84. 2013
    ..disease is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) repeat within the protein huntingtin (Htt)...
  63. ncbi A huntingtin-associated protein enriched in brain with implications for pathology
    X J Li
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 378:398-402. 1995
    ..is an autosomal dominant neurodegenerative disorder caused by an expanding polyglutamine repeat in the IT15 or huntingtin gene...
  64. pmc Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies
    C A Gutekunst
    Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 92:8710-4. 1995
    ..We used polyclonal and monoclonal anti-fusion protein antibodies to identify native huntingtin in rat, monkey, and human...
  65. ncbi HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system
    E E Wanker
    Max Planck Institut fur Molekulare Genetik, Berlin Dahlem, Germany
    Hum Mol Genet 6:487-95. 1997
    We report the discovery of the huntingtin interacting protein I (HIP-I) which binds specifically to the N-terminus of human huntingtin, both in the two-hybrid screen and in in vitro binding experiments...
  66. ncbi Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions
    F Saudou
    Department of Neurology, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 95:55-66. 1998
    The mechanisms by which mutant huntingtin induces neurodegeneration were investigated using a cellular model that recapitulates features of neurodegeneration seen in Huntington's disease...
  67. ncbi Prevalence of Huntington disease in New South Wales in 1996
    E A McCusker
    Neurology Department, Westmead Hospital, Sydney, NSW
    Med J Aust 173:187-90. 2000
    ..To estimate the prevalence of Huntington disease (HD) in New South Wales on Australian Census Day (6 August) 1996...
  68. ncbi Isolation of a 40-kDa Huntingtin-associated protein
    M F Peters
    Division of Neurobiology, Department of Psychiatry, Department of Neuroscience, and The Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Biol Chem 276:3188-94. 2001
    ..disease is caused by an expanded CAG trinucleotide repeat coding for a polyglutamine stretch within the huntingtin protein...
  69. 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...
  70. ncbi Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease
    Guylaine Hoffner
    CNRS UPR 2228, Régulation de la Transcription et Maladies Génétiques, Universite Rene Descartes, 45 Rue des Saints Peres, 75270 Paris Cedex 06, France
    J Cell Sci 115:941-8. 2002
    Huntington's disease results from an expansion of a series of glutamine repeats in the protein huntingtin. We have discovered from immunopurification studies that huntingtin combines specifically with the beta subunit of tubulin...
  71. 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...
  72. ncbi Huntingtin and its role in neuronal degeneration
    Shi Hua Li
    Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA
    Neuroscientist 10:467-75. 2004
    Huntington's disease results from a polyglutamine expansion in the N-terminal region of huntingtin (htt). This abnormality causes protein aggregation and leads to neurotoxicity...
  73. pmc Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity
    Shouqing Luo
    Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, CB2 2XY, England, UK
    J Cell Biol 169:647-56. 2005
    ..Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract in the huntingtin (htt) protein...
  74. ncbi HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin
    Atsushi Iwata
    Department of Biological Sciences, Bio X Program, Stanford University, Stanford, California 94305 5430, USA
    J Biol Chem 280:40282-92. 2005
    ..These data suggest that HDAC6-dependent retrograde transport on microtubules is used by cells to increase the efficiency and selectivity of autophagic degradation...
  75. pmc Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated huntingtin
    Alexandra Benchoua
    URA CEA CNRS 2210, Service Hospitalier Frederic Joliot, MIRCen Program, Département de Recherches Médicales, Direction des Sciences du Vivant, Commissariat a l Energie Atomique CEA, 91401 Orsay Cedex, France
    Mol Biol Cell 17:1652-63. 2006
    ..proteins in striatal neurons that were infected with lentiviral vectors coding for the N-terminus part of huntingtin (Htt) with either a pathological (Htt171-82Q) or physiological (Htt171-19Q) polyglutamine tract...
  76. ncbi Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicity
    Birgit Schilling
    The Buck Institute for Age Research, Novato, California 94945, USA
    J Biol Chem 281:23686-97. 2006
    b>Huntingtin (Htt) is a large protein of 3144 amino acids, whose function and regulation have not been well defined. Polyglutamine (polyQ) expansion in the N terminus of Htt causes the neurodegenerative disorder Huntington disease (HD)...
  77. ncbi Increased caspase-2, calpain activations and decreased mitochondrial complex II activity in cells expressing exogenous huntingtin exon 1 containing CAG repeat in the pathogenic range
    Pritha Majumder
    Saha Institute of Nuclear Physics, 1 AF Bidhan Nagar, Kolkata, 700064, India
    Cell Mol Neurobiol 27:1127-45. 2007
    ..dominant neurodegenerative disease caused by the expansion of polymorphic CAG repeats beyond 36 at exon 1 of huntingtin gene (htt)...
  78. 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)...
  79. 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...
  80. doi Phosphorylation of mutant huntingtin at S421 restores anterograde and retrograde transport in neurons
    Diana Zala
    Institut Curie, Unité Mixte de Recherche 146, F 91405 Orsay, France
    Hum Mol Genet 17:3837-46. 2008
    b>Huntingtin (htt), the protein mutated in Huntington's disease, is a positive regulatory factor for vesicular transport whose function is lost in disease...
  81. pmc Effects of overexpression of huntingtin proteins on mitochondrial integrity
    Hongmin Wang
    Institute for Neurodegenerative Diseases, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA
    Hum Mol Genet 18:737-52. 2009
    ..disease (HD) is caused by an expansion of a CAG trinucleotide sequence that encodes a polyglutamine tract in the huntingtin (Htt) protein...
  82. pmc Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells
    Tamara Ratovitski
    Division of Neurobiology, Department of Psychiatry, Mass Spectrometry and Proteomics Facility, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Biol Chem 284:10855-67. 2009
    b>Huntingtin proteolysis is implicated in Huntington disease pathogenesis, yet, the nature of huntingtin toxic fragments remains unclear...
  83. pmc SCAMP5 links endoplasmic reticulum stress to the accumulation of expanded polyglutamine protein aggregates via endocytosis inhibition
    Jee Yeon Noh
    Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500 712, Korea
    J Biol Chem 284:11318-25. 2009
    ..expression of SCAMP5 augments the formation of ubiquitin-positive and detergent-resistant aggregates of mutant huntingtin (mtHTT)...
  84. pmc The predicted structure of the headpiece of the Huntingtin protein and its implications on Huntingtin aggregation
    Nicholas W Kelley
    Biophysics Program, Stanford University, Stanford, CA 94305, USA
    J Mol Biol 388:919-27. 2009
    ..performed simulated tempering molecular dynamics simulations to study the thermodynamics of the headpiece of the Huntingtin (Htt) protein (N17(Htt))...
  85. 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...
  86. 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...
  87. pmc Secondary structure of Huntingtin amino-terminal region
    Mee Whi Kim
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Structure 17:1205-12. 2009
    ..neurodegenerative disorder resulting from polyglutamine (polyQ) expansion (>36Q) within the first exon of Huntingtin (Htt) protein...
  88. pmc The chaperonin TRiC blocks a huntingtin sequence element that promotes the conformational switch to aggregation
    Stephen Tam
    Department of Biology, BioX Program Stanford University, Stanford, California, USA
    Nat Struct Mol Biol 16:1279-85. 2009
    ..Molecular chaperones modulate the aggregation and toxicity of the huntingtin (Htt) protein by an ill-defined mechanism. Here we determine how the chaperonin TRiC suppresses Htt aggregation...
  89. pmc Huntingtin facilitates polycomb repressive complex 2
    Ihn Sik Seong
    Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
    Hum Mol Genet 19:573-83. 2010
    Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein...
  90. doi Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease
    Jessica M Simpson
    Division of Medical Sciences and Department of Biology, University of Victoria, Victoria, BC, Canada
    Neurobiol Dis 41:249-60. 2011
    ..In this study, we demonstrate decreases in neurogenesis in the DG of YAC128 mice, and these deficits may contribute to the cognitive abnormalities observed in these animals...
  91. pmc Structural features and domain organization of huntingtin fibrils
    Charles W Bugg
    Biology Division, California Institute of Technology, Pasadena, California 91125, USA
    J Biol Chem 287:31739-46. 2012
    Misfolding and aggregation of huntingtin is one of the hallmarks of Huntington disease, but the overall structure of these aggregates and the mechanisms by which huntingtin misfolds remain poorly understood...
  92. ncbi Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons
    M Difiglia
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Neuron 14:1075-81. 1995
    The gene defective in Huntington's disease encodes a protein, huntingtin, with unknown function...
  93. 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...
  94. ncbi SH3 domain-dependent association of huntingtin with epidermal growth factor receptor signaling complexes
    Y F Liu
    Center for Neurological Disease, Brigham and Women s Hospital and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Biol Chem 272:8121-4. 1997
    Based on the presence of multiple proline-rich motifs in the huntingtin sequence, we tested its possible association with epidermal growth factor (EGF) receptor signaling complexes through SH3 domain-containing modules...
  95. ncbi Interaction of huntingtin-associated protein with dynactin P150Glued
    S H Li
    Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Neurosci 18:1261-9. 1998
    b>Huntingtin is the protein product of the gene for Huntington's disease (HD) and carries a polyglutamine repeat that is expanded in HD (>36 units)...
  96. 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 ..
  97. ncbi Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin
    J M Boutell
    Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
    Hum Mol Genet 8:1647-55. 1999
    We detected an interaction of the N-terminus of huntingtin (htt171) with the C-terminal region of the nuclear receptor co-repressor (N-CoR) using the yeast two-hybrid system...
  98. ncbi Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells
    C L Wellington
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Biol Chem 275:19831-8. 2000
    ..disorder caused by CAG expansion that results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt with polyglutamine expansion is proapoptotic in different cell types...
  99. pmc The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription
    J S Steffan
    Department of Biological Chemistry, D240 Medical Sciences I, University of California, Irvine, CA 92697 1700, USA
    Proc Natl Acad Sci U S A 97:6763-8. 2000
    Huntington's Disease (HD) is caused by an expansion of a polyglutamine tract within the huntingtin (htt) protein...
  100. ncbi FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis
    K Hattula
    Institute of Biotechnology, Program in Cellular Biotechnology, P O Box 56 Viikinkaari 9, FIN 00014, University of Helsinki, Finland
    Curr Biol 10:1603-6. 2000
    ..by the death of cortical and striatal neurons, and is the result of an expanded polyglutamine tract in the Huntingtin protein [1]...

Research Grants72

  1. Blocking Huntingtin Toxicity by Intrabody
    Xiao Jiang Li; Fiscal Year: 2006
    ..This proof of principle study will have a broad implication for the treatment of other neurodegeneration diseases that are also caused by misfolded proteins. ..
  2. Developmental effects of 5-HTT genotype on stress reactivity and brain function
    Moriah E Thomason; Fiscal Year: 2010
    ....
  3. David R Corey; Fiscal Year: 2016
    ..Developing compounds to achieve allele-selective inhibition of these genes would widen the therapeutic potential of the approach and offer new perspective on mechanisms. ..
  4. Elaine L Bearer; Fiscal Year: 2016
    ....
  5. Nelly Alia-Klein; Fiscal Year: 2014
    ..Therefore, understanding the basic genetic, neurochemical and neuroanatomical processes associated with aggression is a public health concern. ..
  6. Solomon H Snyder; Fiscal Year: 2016
    ..One involves the small G protein Rhes as a mediator of the neurotoxicity elicited by mutant huntingtin (mHtt)...
  7. RNAi therapy for Huntingtons disease: safety & efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2010
    ..The glutamine expansion in the encoded protein, huntingtin (HTT) confers a toxic gain of function, causing degeneration of neurons in many brain regions, particularly in ..
  8. Nickolay Brustovetsky; Fiscal Year: 2015
    ..disorder associated with the abnormal expansion of CAG triplet that encodes a polyglutamine domain in huntingtin, a 350 kDa protein expressed in various tissues...
  9. RNAi therapy for Huntingtons disease: safety &efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2013
    ..The glutamine expansion in the encoded protein, huntingtin (HTT) confers a toxic gain of function, causing degeneration of neurons in many brain regions, particularly in ..
  10. SANTOSH R D'MELLO; Fiscal Year: 2016
    ..We have observed that HDAC3 interacts with huntingtin protein (Htt), mutation of which causes HD...
  11. Audrey S Dickey; Fiscal Year: 2014
    ..polyglutamine disorder arises from a CAG trinucleotide-repeat expansion mutation in the coding region of the huntingtin (Htt) gene encoding an extended polyglutamine (polyQ) tract...
  12. 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...
  13. Anthony Wing Sang Chan; Fiscal Year: 2014
    ..a viable option as a long-term treatment for Huntington's disease (HD), where expansion of CAG repeats in Huntingtin (HTT) gene results in the degeneration of the majority of striatal neurons...
  14. Xiao Jiang Li; Fiscal Year: 2015
    ..In HD mice that express full-length mutant huntingtin (htt), there is a preferential accumulation of mutant htt in the nuclei of medium spiny neurons in the striatum...
  15. [F-18]Mefway PET to measure 5-HT1A receptors in gene x environment interactions
    BRADLEY CHRISTIAN; Fiscal Year: 2010
    ..This work holds great potential for advancing our knowledge of how environmental experiences interact with genes in the development of anxiety-related illnesses. ..
  16. Depression, Stress, Aging & Proinflammatory Cytokines
    Janice Kiecolt Glaser; Fiscal Year: 2009
    ..The proposed study will expand our knowledge of how genetic polymorphisms interact with environmental stressors to enhance risk for adverse mental and physical health changes. ..
  17. Xiao Jiang Li; Fiscal Year: 2016
    ..protein Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in the N- terminal region of huntingtin (htt)...
  18. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  19. Mervyn J Monteiro; Fiscal Year: 2014
    ..elegans models of HD have shown that overexpression of ubiquilin (ubqln) reduces toxicity of mutant huntingtin (htt) proteins containing expanded polyglutamine repeats...
  20. Dysfunctional Cortico-Limbic Activity and Connectivity in Bipolar Disorder and Li
    Amit Anand; Fiscal Year: 2010
    ..This study will also establish an experimental paradigm to study brain connectivity which could be used to investigate other disorders. ..
  21. ILYA B BEZPROZVANNY; Fiscal Year: 2015
    ..and fatal neurodegenerative disorder caused by polyglutamine repeat (polyQ) expansion in the amino-terminal of Huntingtin (Htt) protein. Striatal medium spiny neurons (MSN) are preferentially affected in HD...
  22. Pharmacologic Treatments in Emerging Adults
    Bankole A Johnson; Fiscal Year: 2012
    ..This innovative and significant study is designed to develop an efficacious pharmacotherapeutic and pharmacogenetic approach that can enhance the efficacy of a brief intervention to treat severe drinking in emerging adults. ..
  23. TRAFFICKING DEFECTS IN HUNTINGTONS DISEASE
    Cynthia McMurray; Fiscal Year: 2009
    ..Further, the data will shed light on a poorly understood pathway of endocytosis that may be involved in the defects. ..
  24. Loss-of-function mechanisms in Huntington's Disease
    Scott O Zeitlin; Fiscal Year: 2013
    ..that is caused by the expansion of a stretch of CAG triplet repeats encoding polyglutamine (polyQ) within huntingtin (htt), the protein product of the HD gene...
  25. Epigenetic Regulation of Serotonin:Relevance to HIV and Methamphetamine Abuse
    GREGORY MICHAEL MILLER; Fiscal Year: 2012
    ....
  26. Functionally Significant Polymorphisms in Serotonin Pathway Genes
    Beverly H Koller; Fiscal Year: 2010
    ..These mice can be used to study the impact of this polymorphism on gene expression, protein function, development, and on the behavioral tests/models known to be sensitive to alterations in this specific pathway in rodents. ..
  27. Anxiety development in 5-HT1A autoreceptor knockout mice, interaction with stress
    Rene Hen; Fiscal Year: 2010
    ....
  28. Pain in Preterm Infants: Development and Effects
    Ruth E Grunau; Fiscal Year: 2012
    ..Further understanding of the role of maternal factors will inform strategies for intervention related to these difficulties. ..
  29. Ramin V Parsey; Fiscal Year: 2015
    ..Ultimately this can lead to novel therapeutics that are better tolerated. We will independently advance our understanding of the molecular pathophysiology of BPD as well as characterize the mechanisms of action of lithium. ..
  30. Serotonin and the Rho Signaling Pathway in Smooth Muscle Cells
    BARRY FANBURG; Fiscal Year: 2010
    ..We believe the overall experiments will provide a better appreciation of 5-HT-related cell signaling pathways that may be operative in PH and may allow new approaches to therapy of this disease. ..
  31. Gene-Environment Interactions in Loneliness and Stress Reactivity in Older Adults
    Turhan Canli; Fiscal Year: 2013
    ..This work is critical for identifying vulnerable individuals and developing tailored interventions. ..
  32. Developmental Origins of Affective Disorders
    MARK SASCHA ANSORGE; Fiscal Year: 2012
    ..Finally, our fourth aim will investigate the causal involvement of raphe activity in the etiology of depression and anxiety-like behaviors. ..
  33. Neurobiological Bases of Placebo Response in Major Depressive Disorder
    Cristina Cusin; Fiscal Year: 2013
    ..The understanding of the neurobiological bases of placebo effect, and how to modulate it, would potentially lead to the development of new treatments for depression and profoundly modify the conduct of clinical trials. ..
  34. Albert R La Spada; Fiscal Year: 2016
    ..DESCRIPTION (provided by applicant): Recent published studies by our laboratory and others have shown that mutant huntingtin (htt)-mediated transcription dysregulation of PGC-11 disrupts expression of genes necessary for normal ..
  35. Gwenn S Smith; Fiscal Year: 2015
    ..Having accomplished the specific aims, the data obtained will support future 5-HT pharmacologic intervention studies in aMCI-MD, as well as the investigation of other molecular mechanisms associated with the neurobiological model. ..
  36. 5HTT and 5-HT2A Receptors in Impulsive Aggression and Effects of Fluoxetine
    Larry J Siever; Fiscal Year: 2012
    ..These studies will help our understanding of an important brain chemical, serotonin, which is related to aggression, and how it is affected by antidepressants that increase serotonin. ..
  37. Functionally Significant Polymorphisms in Serotonin Pathway Genes
    Beverly Koller; Fiscal Year: 2009
    ..These mice can be used to study the impact of this polymorphism on gene expression, protein function, development, and on the behavioral tests/models known to be sensitive to alterations in this specific pathway in rodents. ..
  38. RNA interference therapy for Huntington's disease: studies in non-human primates
    Beverly L Davidson; Fiscal Year: 2010
    ..HD is a fatal, genetic disorder caused by mutations in HTT, which encodes huntingtin (HTT), and affects approximately 30,000 people in the United States alone...
  39. Hoon Ryu; Fiscal Year: 2015
    ..progressive autosomal-dominant neurological disorder caused by expanded CAG repeats coding for glutamine in the huntingtin (Htt) gene but it is not known how this mutation causes neurodegeneration...
  40. Monoallelic repair of expanded huntingtin by trans-splicing
    Hansjorg Rindt; Fiscal Year: 2011
    ..neurodegenerative disorder which is caused by polyglutamine expansion in the amino-terminus of huntingtin (HTT). It is characterized by progressive movement disorder, cognitive decline and psychiatric disturbances...
  41. Russell L Margolis; Fiscal Year: 2014
    ..HD is caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Substantial advances have been made into understanding the neurobiology of HD...
  42. Beverly L Davidson; Fiscal Year: 2014
    ..We will now test the capabilities of these promoters to drive RNAi in a disease responsive manner in vitro and in vivo. ..
  43. Reversible conditional models for Huntington's disease
    Scott O Zeitlin; Fiscal Year: 2012
    ..that is caused by the expansion of a CAG triplet repeat encoding a stretch of polyglutamine (polyQ) within Huntingtin (Htt), the protein product of the HD gene...
  44. Zinc-Finger Nuclease- Mediated Repair of Disease-Causing Triplet CAG Repeats
    David A Mittelman; Fiscal Year: 2013
    ....
  45. Polycomb-mediated epigenetic mechanisms in neurodegeneration and aging brain
    Hiroko Yano; Fiscal Year: 2013
    ..We are interested in neuronal death in HD, a process driven by abnormal polyglutamine expansions in the huntingtin protein (Htt)...
  46. ELLA R BOSSY-WETZEL; Fiscal Year: 2016
    ..HD) is a neurodegenerative disease caused by an abnormal expansion of a poly- glutamine (poly-Q) repeats in huntingtin (Htt), a 350 kDa protein. People with HD experience chorea, dementia, and psychiatric disturbances...
  47. Regulation of BimEL phosphorylation in the pathogenesis of Huntington's disease
    Jianning Wei; Fiscal Year: 2012
    ..Our long-term goal is to characterize the molecular basis for mutant huntingtin (mhtt)-induced toxicity, which can lead us to identify potential targets for HD treatment...
  48. XIAP Gene Therapy in Huntington's Disease
    Michael G Kaplitt; Fiscal Year: 2013
    ..HD is caused by a pathological expansion of polyglutamine repeats in the Huntingtin gene (mhtt), resulting in the eventual loss predominantly of striatal medium spiny neurons although dysfunction ..
  49. The Role of Microglia and the Kynurenine Pathway in Huntington's Disease
    Paul J Muchowski; Fiscal Year: 2012
    ..HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract in the protein huntingtin (htt)...
  50. Huntington's Disease: Analysis of Proteolysis
    ROBERT NORMAN O'BRIEN; Fiscal Year: 2013
    ..HD is caused by expansion of a CAG trinucleotide repeat in the first exon of the huntingtin (HTT) gene and results in translation of a protein that contains an enlarged CAG- encoded polyglutamine (polyQ) ..
  51. Stanley N Cohen; Fiscal Year: 2016
    ..The disease results from mutational expansion of the number of repeats of the trinucleotide CAG in the huntingtin (htt) gene, resulting in production of a defective Htt protein that forms insoluble aggregates in brain cells...
  52. Cell-specific translational profiling in Huntington's Disease mouse models
    ROBERT JONATHAN FENSTER; Fiscal Year: 2012
    ..provided by applicant): Huntington's Disease (HD) has been linked to an expansion of CAG repeats in the huntingtin (htt) gene...
  53. RONALD B WETZEL; Fiscal Year: 2014
    ..The full length Huntingtin protein has been very challenging to make and to work with, while the more manageable N- terminal fragment, ..
  54. Huntington's Disease and the Striatum
    Michelle E Ehrlich; Fiscal Year: 2010
    ..disease (HD) is an autosomal dominant disorder caused by a mutation in the IT15 gene encoding the protein huntingtin (htt)...
  55. High throughput assay development for Huntington?s Disease
    RONALD B WETZEL; Fiscal Year: 2010
    ..of Huntington's disease is a triplet expansion in the DNA leading to an inherited gene for the protein huntingtin (htt) with an equivalent expansion of a polyglutamine (polyQ) repeat...
  56. Role of Huntington's Disease Protein in Post-Transcriptional Gene Silencing
    Naoko Tanese; Fiscal Year: 2013
    ..neurodegenerative disorder caused by an expanded poly-glutamine (polyQ) tract within the amino-terminus of the huntingtin (Htt) protein, whose cellular function remains controversial...
  57. Marian DiFiglia; Fiscal Year: 2014
    ..In vivo validation of increasing Rab11 activity will justify a drug discovery effort to screen for small molecules that raise the activity of Rab11 as a therapy for HD. ..
  58. Huntington's Disease and Neurogenesis
    Lisa M Ellerby; Fiscal Year: 2012
    ..We are developing a potential therapy to protect neurons or replace them in Huntington's disease. ..
  59. Jason E Gestwicki; Fiscal Year: 2016
    ..ATP turnover favored degradation of multiple Hsp70 substrates, such as tau and polyglutamine (polyQ) expanded huntingtin (polyQ-Htt) and androgen receptor (polyQ-AR), while stimulating activity led to substrate accumulation and ..
  60. EMILY A ANDRE; Fiscal Year: 2014
    ..Although the mutation that causes HD, an expansion of CAG repeats encoding polyglutamine (polyQ) in the Huntingtin (Htt) protein, was discovered 20 years ago, there is still no effective treatment or cure for HD...
  61. Frank M Longo; Fiscal Year: 2014
    ..Positive results obtained here would be the first validation that p75NTR is an effective therapeutic target for an HD model and could fast track LM11A-31 into HD clinical testing. ..
  62. A Drosophila model to investigate prion-like transmission of Huntington's disease
    MARGARET MARIE PEARCE; Fiscal Year: 2012
    ..expansion of a polyglutamine (polyQ) tract near the N-terminus of the ubiquitously-expressed, cytosolic protein huntingtin (Htt)...
  63. Brain serotonin and angiotensin II systems in migraine
    JOSE TERRON; Fiscal Year: 2007
    ..5-HT content will be measured by HPLC in brain homogenates. ..
  64. CEHCs as Therapeutics for Huntington's Disease
    ELAINE BENAKSAS SCHWARTZ; Fiscal Year: 2005
    ..HD progression in an accepted mouse genetic model, the R6/2 mouse that expresses the first exon of mutant human huntingtin (Htt) containing a pathogenic polyglutamine expansion...
  65. Mechanism of Fast Axonal Transport Inhibition by PolyQ-Expanded Huntingtin
    Sarah Pollema; Fiscal Year: 2009
    ..single gene disease displays dominant inheritance, and is thought to involve a toxic gain of function in the Huntingtin (Htt) protein...
  66. Genetic and Caregiving Effects on Disordered Attachment
    Karlen Lyons Ruth; Fiscal Year: 2005
    ..This research will be carried out primarily in Budapest, Hungary, at the laboratories of Drs. Sasvari-Szekely and Gervai as an extension of Dr. Lyons-Ruth's U.S. grant, NIH R01 MH 062030. ..