Blair R Leavitt

Summary

Affiliation: University of British Columbia
Country: Canada

Publications

  1. ncbi Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, British Columbia Research Institute for Children s and Women s Health, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Exp Neurol 196:266-72. 2005
  2. 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
  3. ncbi Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse models
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 21:444-55. 2006
  4. ncbi Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin
    Rona K Graham
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada
    Cell 125:1179-91. 2006
  5. ncbi Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Neurobiol Dis 26:189-200. 2007
  6. pmc Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z 4H4, BC, Canada
    BMC Neurosci 7:80. 2006
  7. pmc Differential susceptibility to excitotoxic stress in YAC128 mouse models of Huntington disease between initiation and progression of disease
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    J Neurosci 29:2193-204. 2009
  8. pmc Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Proc Natl Acad Sci U S A 102:11402-7. 2005
  9. doi Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A
    Martina Metzler
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Neurosci 30:14318-29. 2010
  10. pmc Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis
    Kristina Becanovic
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 19:1438-52. 2010

Detail Information

Publications55

  1. ncbi Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, British Columbia Research Institute for Children s and Women s Health, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Exp Neurol 196:266-72. 2005
    ..Overall, this work demonstrates the feasibility of experimental therapeutics in the YAC128 mouse model and suggests that experiments in these mice may be predictive for future human clinical trials...
  2. 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
    ....
  3. ncbi Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse models
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 21:444-55. 2006
    ..These results provide clear evidence in vivo supporting a more severe phenotype associated with increased levels of mutant huntingtin as seen in homozygotes for HD...
  4. ncbi Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin
    Rona K Graham
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC V5Z 4H4, Canada
    Cell 125:1179-91. 2006
    ....
  5. ncbi Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Neurobiol Dis 26:189-200. 2007
    ..Importantly, the demonstration of penetrance across all three strains permits examining the effect of specific genes on the phenotypic severity in YAC128 mice without necessarily backcrossing onto the FVB/N strain background...
  6. pmc Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, V5Z 4H4, BC, Canada
    BMC Neurosci 7:80. 2006
    ....
  7. pmc Differential susceptibility to excitotoxic stress in YAC128 mouse models of Huntington disease between initiation and progression of disease
    Rona K Graham
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    J Neurosci 29:2193-204. 2009
    ..These data highlight the dynamic nature of the mutant htt-mediated excitotoxic phenotype and suggests that therapeutic approaches to HD may need to be altered, depending on the stage and development of the disease...
  8. pmc Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions
    Elizabeth J Slow
    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Proc Natl Acad Sci U S A 102:11402-7. 2005
    ....
  9. doi Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A
    Martina Metzler
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada
    J Neurosci 30:14318-29. 2010
    ....
  10. pmc Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis
    Kristina Becanovic
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Hum Mol Genet 19:1438-52. 2010
    ..Further study of these genes may unravel novel pathways contributing to HD pathogenesis. DDBJ/EMBL/GenBank accession no: GSE19677...
  11. ncbi Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics and British Columbia Research Institute for Women and Children s Health, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurochem 95:210-20. 2005
    ..While the exact mechanism responsible for the beneficial effects of cystamine in YAC128 mice is uncertain, our findings suggest that cystamine is neuroprotective and may be beneficial in the treatment of HD...
  12. ncbi Testicular degeneration in Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Ave, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 26:512-20. 2007
    ..Understanding the pathogenesis of HD in the testis may reveal common critical pathways which lead to degeneration in both the brain and testis...
  13. ncbi Body weight is modulated by levels of full-length huntingtin
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Hum Mol Genet 15:1513-23. 2006
    ..Overall, we demonstrate that increased levels of both wild-type and mutant full-length htt are associated with increased body weight...
  14. 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
    ....
  15. ncbi HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis
    Roshni R Singaraja
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Hum Mol Genet 11:2815-28. 2002
    ..Our findings suggest that decreased interaction between htt and HIP14 could contribute to the neuronal dysfunction in HD by perturbing normal intracellular transport pathways in neurons...
  16. ncbi Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, and Centre for Molecular Medicine and Thrapeutics, British Columbia Research Institute for Children s and Women s Health, Vancouver, Canada
    Hum Mol Genet 14:3823-35. 2005
    ....
  17. ncbi Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease
    Jacqueline Shehadeh
    Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
    Neurobiol Dis 21:392-403. 2006
    ..Our results suggest that increased NMDAR signaling plays a major role in enhanced excitotoxic MSN death in this HD mouse model...
  18. 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
    ..We demonstrate that the levels of FL htt influence IGF-1 expression in striatal tissues. Our data identify a novel function for FL htt in influencing IGF-1 expression...
  19. ncbi Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington's disease
    Melinda M Zeron
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Mol Cell Neurosci 25:469-79. 2004
    ..Agents that improve mitochondrial function or inhibit the permeability transition may eliminate increased caspase activation and cell death associated with enhanced NMDAR activity in HD...
  20. ncbi Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease
    Cheryl L Wellington
    Centre for Molecular Medicine and Therapeutics, British Columbia Children s and Women s Hospital, Vancouver, British Columbia, Canada
    J Neurosci 22:7862-72. 2002
    ....
  21. ncbi Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease
    Jeremy M Van Raamsdonk
    Department of Medical Genetics, University of British Columbia, Vancouver, Canada
    Hum Mol Genet 14:1379-92. 2005
    ....
  22. pmc CAG-encoded polyglutamine length polymorphism in the human genome
    Stefanie L Butland
    UBC Bioinformatics Centre, Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    BMC Genomics 8:126. 2007
    ....
  23. ncbi Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease
    Lijun Li
    Kinsmen Laboratories, Department of Psychiatry, University of British Columbia, 4N3 2255 Westbrook Mall, BC, Vancouver, Canada V6T 1Z3
    Neurobiol Aging 24:1113-21. 2003
    ..Potentiation of NR2B-containing NMDAR current in striatal MSNs expressing mutant huntingtin may help explain the exquisite vulnerability of these neurons to degeneration in HD...
  24. 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
    ....
  25. pmc Expression analysis of novel striatal-enriched genes in Huntington disease
    Gelareh Mazarei
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada
    Hum Mol Genet 19:609-22. 2010
    ..The identification of novel striatal-enriched genes with altered expression in HD offers new avenues of study, leading towards a better understanding of specific pathways involved in the selective degeneration of striatal neurons in HD...
  26. doi Cystamine and ethyl-eicosapentaenoic acid treatment fail to prevent malonate-induced striatal toxicity in mice
    Saskia N Sivananthan
    Department of Medical Genetics and Centre for Molecular Medicine and Therapeutics, University of British Columbia, British Columbia, Vancouver, Canada
    Neurobiol Aging 32:2326.e1-4. 2011
    ..Our findings suggest that this toxic model is not reflective or predictive of findings in genetic mouse models, and may not be useful as a preclinical screen for HD therapeutics...
  27. doi Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease
    Sonia Franciosi
    Centre for Molecular Medicine and Therapeutics and Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 45:438-49. 2012
    ..This study identifies age-dependent increases in microglial activation and angiogenesis in YAC128 at 12 months. Peripheral inflammation induced by chronic LPS causes similar changes but does not influence the HD phenotype in YAC128 mice...
  28. pmc Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease
    Ian R Mackenzie
    Department of Pathology, University of British Columbia, Vancouver, BC, Canada
    BMC Neurol 6:32. 2006
    ..The genetic basis of familial FTLD-U is currently not known, however the presence of NII suggests that a subset of cases may represent a polyglutamine expansion disease...
  29. pmc Satellog: a database for the identification and prioritization of satellite repeats in disease association studies
    Perseus I Missirlis
    Genome Sciences Centre, BC Cancer Agency, Suite 100, 570 West 7th Ave, Vancouver, BC, V5Z 4S6, Canada
    BMC Bioinformatics 6:145. 2005
    ..Here we present Satellog, a database that catalogs all pure 1-16 repeat unit satellite repeats in the human genome along with supplementary data. Satellog analyzes each pure repeat in UniGene clusters for evidence of repeat polymorphism...
  30. ncbi Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood
    Rebecca S Devon
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children and Women s Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 18:243-57. 2005
    ..Additionally, the product of a second, widely expressed gene, ALS2 C-terminal like (ALS2CL), may subserve or modulate some of the functions of alsin as an activator of Rab and Rho GTPases...
  31. doi Synaptic dysfunction in progranulin-deficient mice
    Terri L Petkau
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children s and Women s Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Dis 45:711-22. 2012
    ..We conclude that progranulin deficiency leads to reduced synaptic connectivity and impaired plasticity, which may contribute to FTD pathology in human patients...
  32. doi The clinical and genetic features of Huntington disease
    Aaron Sturrock
    Department of Medical Genetics, University of British Columbia UBC, Vancouver, British Columbia, Canada
    J Geriatr Psychiatry Neurol 23:243-59. 2010
    ..In this review, we seek to provide an overview of the clinical and genetic features of HD together with a summary of clinical research at this time...
  33. doi A systematic review and meta-analysis of clinical variables used in Huntington disease research
    Sonia Franciosi
    Center for Molecular Medicine and Therapeutics and Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Mov Disord 28:1987-94. 2013
    ..A list of variables, references used in this meta-analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications. © 2013 International Parkinson and Movement Disorder Society. ..
  34. doi 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...
  35. doi p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin
    Dagmar E Ehrnhoefer
    Centre for Molecular Medicine and Therapeutics CMMT, Department of Medical Genetics, CFRI, University of British Columbia, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    Hum Mol Genet 23:717-29. 2014
    ..Furthermore, these results suggest that this pathway is activated both within and outside the CNS in HD and may contribute to both loss of CNS neurons and muscle atrophy. ..
  36. doi Age-dependent alterations of the kynurenine pathway in the YAC128 mouse model of Huntington disease
    Gelareh Mazarei
    Centre for Molecular Medicine and Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurochem 127:852-67. 2013
    ..Striatally specific induction of Ido1 and downstream KP alterations suggest involvement in HD pathogenesis, and should be taken into account in future therapeutic developments for HD. ..
  37. ncbi Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease
    Edmond Y W Chan
    Center for Molecular Medicine and Therapeutics, Department of Medical Genetics, Children s and Women s Hospital, University of British Columbia, Vancouver, British Columbia, Canada, V5H 4H4
    Hum Mol Genet 11:1939-51. 2002
    ..Furthermore, our findings suggest that short N-terminal fragments of mutant htt might be responsible for the gene expression alterations observed in human HD brain...
  38. doi Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice
    Terri L Petkau
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Children s and Women s Hospital, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4
    Neurobiol Aging 34:2548-50. 2013
    ..Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study...
  39. ncbi Chapter 15 Juvenile amyotrophic lateral sclerosis
    Paul Orban
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics and British Columbia Research Institute for Women and Children s Health, University of British Columbia, Vancouver, BC, Canada
    Handb Clin Neurol 82:301-12. 2007
    ..Acquired disorders that must also be consid-ered include heavy metal intoxications (especially lead), multifocal motor neuropathy, paraneoplastic syndromes, vitamin deficiencies (B12) and infections (HTLV-II, HIV and poliomyelitis)...
  40. doi Postnatal muscle modification by myogenic factors modulates neuropathology and survival in an ALS mouse model
    Kevin H J Park
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    Nat Commun 4:2906. 2013
    ....
  41. doi Progranulin promotes activation of microglia/macrophage after pilocarpine-induced status epilepticus
    Shanshan Zhu
    Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada
    Brain Res 1530:54-65. 2013
    ..Our findings suggest that status epilepticus induces PGRN expression, and that PGRN potentiates but is not required for seizure-induced microglia/macrophage activation. ..
  42. ncbi Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease
    Melinda M Zeron
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, 221 84, Lund, Sweden
    Neuron 33:849-60. 2002
    ..Moreover, increased NMDA-evoked current amplitude and caspase-3 activity were observed in transgenic striatal neurons. Our data support a role for NR2B-subtype NMDAR activation as a trigger for selective neuronal degeneration in HD...
  43. ncbi Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines
    Alexander V Panov
    Department of Neurology, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, Georgia 30322, USA
    Nat Neurosci 5:731-6. 2002
    ..Thus, mitochondrial calcium abnormalities occur early in HD pathogenesis and may be a direct effect of mutant huntingtin on the organelle...
  44. 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
    ....
  45. pmc A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease
    Maria Björkqvist
    Neuronal Survival Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, S 221 00 Lund, Sweden
    J Exp Med 205:1869-77. 2008
    ..Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD...
  46. 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
    ..This novel non-receptor-mediated pathway for activating caspase-8 might contribute to neuronal death in Huntington disease...
  47. ncbi Long-term lentiviral-mediated expression of ciliary neurotrophic factor in the striatum of Huntington's disease transgenic mice
    Diana Zala
    Institute of Neuroscience, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland
    Exp Neurol 185:26-35. 2004
    ..Further studies are, however, needed to investigate the intracellular signaling pathways mediating the long-term effects of CNTF expression on dopamine signaling, glial cell activation and how these changes may affect HD pathology...
  48. ncbi Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage
    Alexandre Kuhn
    Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
    Hum Mol Genet 16:1845-61. 2007
    ....
  49. 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
    ..These data identify a new mechanism by which mutation of huntingtin causes loss of transcription of neuronal genes...
  50. ncbi Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice
    Paolo Guidetti
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Neurobiol Dis 23:190-7. 2006
    ....
  51. ncbi Depletion of wild-type huntingtin in mouse models of neurologic diseases
    Yu Zhang
    Neuroapoptosis Laboratory, Department of Neurosurgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    J Neurochem 87:101-6. 2003
    ..We propose that in HD, in addition to a toxic gain-of-function of mutant huntingtin, a parallel depletion of wild-type huntingtin results in a detrimental loss-of-function, playing an important role in disease progression...
  52. ncbi Striatal neurochemical changes in transgenic models of Huntington's disease
    Marjorie A Ariano
    Department of Neuroscience, The Chicago Medical School, North Chicago, Illinois 60064, USA
    J Neurosci Res 68:716-29. 2002
    ..These findings suggest modifications in the striatal DA system and that its downstream signaling through cyclic AMP mechanisms is disrupted severely in HD following onset of motor symptoms...
  53. ncbi Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates
    Annette Dalrymple
    Proteome Sciences plc, Cobham, Surrey, United Kingdom
    J Proteome Res 6:2833-40. 2007
    ..Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers...
  54. ncbi Cocaine- and amphetamine-regulated transcript is increased in Huntington disease
    Maria Björkqvist
    Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund, Sweden
    Mov Disord 22:1952-4. 2007
    ..Increased CART levels in HD therefore hold promise as a biomarker as well as a potential pathogenic mediator of symptoms...
  55. ncbi Treatment of YAC128 mice and their wild-type littermates with cystamine does not lead to its accumulation in plasma or brain: implications for the treatment of Huntington disease
    John T Pinto
    Burke Medical Research Institute, White Plains, New York, New York 10605, USA
    J Neurochem 94:1087-101. 2005
    ..These findings suggest that cystamine is not directly involved in mitigating HD but that increased brain cysteine or uncharacterized sulfur metabolites may be responsible...