Jang Ho Cha
Affiliation: Harvard University
- Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical "disconnection"H Diana Rosas
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Neuroimage 49:2995-3004. 2010..Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing...
- Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS studyJian Liang Li
Department of Neurology, Boston University School of Medicine, Boston, MA, USA
BMC Med Genet 7:71. 2006....
- Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's diseaseJ H Cha
Department of Neurology, Massachusetts General Hospital, Boston 02114, USA
Philos Trans R Soc Lond B Biol Sci 354:981-9. 1999..These results suggest that (i) receptor decreases precede, and therefore might contribute to, the development of clinical symptoms, and (ii) altered transcription of specific genes might be a key pathological mechanism in HD...
- Transcriptional signatures in Huntington's diseaseJang Ho J Cha
MassGeneral Institute for Neurodegenerative Disease, 114 16th Street B114 2000, Charlestown, MA 02129 4404, USA
Prog Neurobiol 83:228-48. 2007..In the future, gene expression profiling will be used as a readout in clinical trials aimed at correcting transcriptional dysregulation in Huntington's disease...
- Finding diamonds in the rubbleJang Ho J Cha
Exp Neurol 205:1-4. 2007
- Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington diseaseCaroline L Benn
Mass General Institute for Neurodegenerative Disease, Charlestown, Massachusetts, USA
J Neuropathol Exp Neurol 69:817-27. 2010..Thus, the therapeutic effects of environmental enrichment likely contribute to decreasing aggregated polyglutamine protein levels without exerting strong effects on gene expression...
- Dopamine release is impaired in a mouse model of DYT1 dystoniaAygul Balcioglu
MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
J Neurochem 102:783-8. 2007..The defect in DA release as observed may contribute to the abnormalities in motor learning as previously documented in this transgenic mouse model, and may contribute to the clinical symptoms of the human disorder...
- Diffusion-weighted magnetic resonance imaging abnormalities in Bartonella encephalopathyAneesh B Singhal
Department of Neurology, Massachusetts General Hospital, Biogen, Inc MAP, Boston, USA
J Neuroimaging 13:79-82. 2003..In patients with unexplained, refractory seizures, the presence of DWI abnormalities warrants a search for unusual infectious or inflammatory disorders, like Bartonella encephalitis...
- Mechanisms of distribution of mouse beta-galactosidase in the adult GM1-gangliosidosis brainM L D Broekman
Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
Gene Ther 16:303-8. 2009..In addition, we found evidence of axonal transport of vector-encoded mRNA...
- Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor proteinJ H Cha
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
Neurobiol Dis 8:90-102. 2001..These data suggest that mutant APP overexpression or age-related amyloid deposition produce a subtle specific alteration in hippocampal glutamate receptors with aging...
- Huntingtin modulates transcription, occupies gene promoters in vivo, and binds directly to DNA in a polyglutamine-dependent mannerCaroline L Benn
Department of Neurology and Center for Interdisciplinary Informatics, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
J Neurosci 28:10720-33. 2008..Together, these findings suggest mutant Htt modulates gene expression through abnormal interactions with genomic DNA, altering DNA conformation and transcription factor binding...
- Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulationMee Ohk Kim
MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Neurosci 28:3947-57. 2008..These findings also provide a rationale for targeting histone monoubiquitylation for therapy in HD...
- 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 dosageAlexandre Kuhn
Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
Hum Mol Genet 16:1845-61. 2007....
- Histones associated with downregulated genes are hypo-acetylated in Huntington's disease modelsGhazaleh Sadri-Vakili
Department of Neurology, MassGeneral Institute for NeurodegenerativeDisease, Massachusetts General Hospital, B114 2000, 114 16th Street, Charlestown, MA 02129 4404, USA
Hum Mol Genet 16:1293-306. 2007..Nevertheless, treatment with HDAC inhibitors corrects mRNA abnormalities through modification of histone proteins and may prove to be of therapeutic value in HD...
- Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's diseaseEdmond 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...
- Histone deacetylase inhibitors: a novel therapeutic approach to Huntington's disease (complex mechanism of neuronal death)Ghazaleh Sadri-Vakili
Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, 114 16th Street B114 2001, Charlestown, MA 02129 4404, USA
Curr Alzheimer Res 3:403-8. 2006..In this review we discuss a number of studies that use HDAC inhibitors as therapeutic agents in HD models. These studies demonstrate that HDAC inhibitors are a promising therapeutic approach for the treatment of HD...
- Sp1 is up-regulated in cellular and transgenic models of Huntington disease, and its reduction is neuroprotectiveZhihua Qiu
Massachusetts General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA
J Biol Chem 281:16672-80. 2006..Our data suggest that enhancement of transcription factor Sp1 contributes to the pathology of HD and demonstrates that its suppression is beneficial...
- Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington's diseaseGeorge J Yohrling IV
Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Neurochem 82:1416-23. 2002..The presymptomatic inhibition of TPH activity in the R6/2 mice may help explain the functional consequences of HD and provide insights into new targets for pharmacotherapy...
- Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic miceTeresa Gomez-Isla
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Neurobiol Aging 24:245-58. 2003..Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line...
- Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's diseaseAlice S Chen-Plotkin
MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital B114 2000, 114 16th Street, Charlestown, MA 02129 4404, USA
Neurobiol Dis 22:233-41. 2006..Moreover, the altered binding seen with Sp1 is not found with another transcription factor, NF-Y. These findings suggest that mutant huntingtin dissociates Sp1 from target promoters, inhibiting transcription of specific genes...
- Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's diseaseCaroline 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...
- Mutant huntingtin increases nuclear corepressor function and enhances ligand-dependent nuclear hormone receptor activationGeorge J Yohrling
Department of Neurology, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, Charlestown 02129, USA
Mol Cell Neurosci 23:28-38. 2003..In vitro binding data shows that TR binds to HD53Q in the presence of ligand. Taken together these data suggest that Htt may function as a transcriptional coactivator of nuclear hormone receptors...
- Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathologyGeorge J Yohrling
Department of Neurology, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, 114 16th Street, B114 2000, Charlestown, MA 02129 4404, USA
Brain Res Mol Brain Res 119:28-36. 2003..These findings implicate abnormalities in dopamine neurotransmission in HD and may provide new insights into targets for pharmacotherapy...
- A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS studyJian Liang Li
Department of Neurology, Boston University School of Medicine, and Bioinformatics Program, School of Public Health, Boston University, Boston, MA, USA
Am J Hum Genet 73:682-7. 2003..Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD...
- 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosisWendy J Broom
Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Amyotroph Lateral Scler 9:229-37. 2008..Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations...
- Neurotransmitter receptor analysis in transgenic mouse modelsCaroline L Benn
Mass General Institute for Neurodegenerative Disease and Department of Neurolofy, Massachusetts General Hospital, Charlestown, USA
Methods Mol Biol 277:231-60. 2004..With receptor binding and ISH, one can obtain quantitative region-specific assessments of neurotransmitter receptor alteration, a key pathologic event in HD pathogenesis...
- Chromatin immunoprecipitation technique for study of transcriptional dysregulation in intact mouse brainMelissa W Braveman
Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, USA
Methods Mol Biol 277:261-76. 2004..ChIP applied to whole-mouse brain can thus offer a window into mechanisms of transcriptional dysregulation...
- The paradigm of Huntington's disease: therapeutic opportunities in neurodegenerationJulie Leegwater-Kim
Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
NeuroRx 1:128-38. 2004..HD thus continues to serve as a paradigmatic disorder, with basic bench research generating clinically relevant insights and stimulating the development of therapeutic human trials...
- Mechanisms of disease: Histone modifications in Huntington's diseaseGhazaleh Sadri-Vakili
MassGeneral Institute for Neurodegenerative Disease, Boston, MA, USA
Nat Clin Pract Neurol 2:330-8. 2006..In addition, we discuss how these histone modifications not only lead to pathogenesis, but might also provide a novel therapeutic strategy for treating this devastating disease...