Christopher A Ross

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. doi request reprint Huntington's disease: from molecular pathogenesis to clinical treatment
    Christopher A Ross
    Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Lancet Neurol 10:83-98. 2011
  2. pmc ATF3 plays a protective role against toxicity by N-terminal fragment of mutant huntingtin in stable PC12 cell line
    Yideng Liang
    Division of Neurobiology, Department of Psychiatry, The Johns Hopkins University School of Medicine, CMSC 8 121, 600 N Wolfe St, Baltimore, MD 21287, USA
    Brain Res 1286:221-9. 2009
  3. pmc Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration
    Wanli W Smith
    Department of Psychiatry, Division of Neurobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 102:18676-81. 2005
  4. pmc Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease
    Jing Jin
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Neurochem 125:410-9. 2013
  5. ncbi request reprint Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin
    Haibing Jiang
    Division of Neurobiology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurobiol Dis 23:543-51. 2006
  6. pmc Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
    Wenzhen Duan
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 30:312-22. 2008
  7. pmc Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model
    Wanli W Smith
    Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 19:2087-98. 2010
  8. 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
  9. ncbi request reprint Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells
    Wanli W Smith
    Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:5544-52. 2005
  10. ncbi request reprint Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin
    Yuji Tanaka
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 21:381-91. 2006

Detail Information

Publications85

  1. doi request reprint Huntington's disease: from molecular pathogenesis to clinical treatment
    Christopher A Ross
    Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Lancet Neurol 10:83-98. 2011
    ..Thus, Huntington's disease is also emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset...
  2. pmc ATF3 plays a protective role against toxicity by N-terminal fragment of mutant huntingtin in stable PC12 cell line
    Yideng Liang
    Division of Neurobiology, Department of Psychiatry, The Johns Hopkins University School of Medicine, CMSC 8 121, 600 N Wolfe St, Baltimore, MD 21287, USA
    Brain Res 1286:221-9. 2009
    ..These results indicated that ATF3 plays a critical role in toxicity induced by mutant Htt-N63 and may lead to a useful therapeutic target...
  3. pmc Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration
    Wanli W Smith
    Department of Psychiatry, Division of Neurobiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 102:18676-81. 2005
    ....
  4. pmc Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease
    Jing Jin
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Neurochem 125:410-9. 2013
    ..Our results suggest that modifying the PPAR-γ pathway plays a beneficial role in rescuing motor function as well as glucose metabolic abnormalities in HD...
  5. ncbi request reprint Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin
    Haibing Jiang
    Division of Neurobiology, Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurobiol Dis 23:543-51. 2006
    ..CBP overexpression rescued both acetylated histone levels and cell toxicity. These data suggest that CBP dysfunction and altered gene transcription contribute to mutant htt-induced neurotoxicity...
  6. pmc Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease
    Wenzhen Duan
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 30:312-22. 2008
    ..Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients...
  7. pmc Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model
    Wanli W Smith
    Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 19:2087-98. 2010
    ..These studies demonstrate that synphilin-1 can diminish the severity of alpha-synucleinopathy and play a neuroprotective role against A53T alpha-synuclein toxicity in vivo...
  8. 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
    ..These data suggest that cleavage of huntingtin at residue Arg(167) may mediate mutant huntingtin toxicity in Huntington disease...
  9. ncbi request reprint Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells
    Wanli W Smith
    Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:5544-52. 2005
    ..These results indicate that phosphorylation of alpha-synuclein at S129 may be important for the formation of inclusions in PD and related alpha synucleinopathies...
  10. ncbi request reprint Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin
    Yuji Tanaka
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 21:381-91. 2006
    ..The data suggest that proteolytic processing could be a part of the pathogenesis of HD, potentially representing an attractive therapeutic target...
  11. pmc Structural MRI detects progressive regional brain atrophy and neuroprotective effects in N171-82Q Huntington's disease mouse model
    Yong Cheng
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neuroimage 56:1027-34. 2011
    ..Our present studies provide the first evidence that longitudinal structural MRI measures can detect the therapeutic effect in HD mice, suggesting that such measures in brain could be valuable biomarkers in HD clinical trials...
  12. pmc A mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice
    Veronica F Colomer Gould
    Department of Psychiatry, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer Research Building, Room 4 158, Baltimore, MD 21287, USA
    Neurobiol Dis 27:362-9. 2007
    ..Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190...
  13. ncbi request reprint Kinase activity of mutant LRRK2 mediates neuronal toxicity
    Wanli W Smith
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
    Nat Neurosci 9:1231-3. 2006
    ..These data elucidate the pathogenesis of LRRK2-linked Parkinson disease, potentially illuminate mechanisms of sporadic Parkinson disease and suggest therapeutic targets...
  14. pmc Tiagabine is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's disease
    Naoki Masuda
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8 121, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 30:293-302. 2008
    ..These results suggest that tiagabine may have beneficial effects in the treatment of HD. Because tiagabine is an FDA-approved drug, it may be a promising candidate for future clinical trials for the treatment of HD...
  15. pmc Striatal neuronal loss correlates with clinical motor impairment in Huntington's disease
    Zhihong Guo
    Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mov Disord 27:1379-86. 2012
    ..Our findings suggest that neuronal loss and atrophy in striatum and neuronal loss in subthalamic nuclei contribute specifically to the motor impairment of HD, but not to chorea...
  16. doi request reprint Age, CAG repeat length, and clinical progression in Huntington's disease
    Adam Rosenblatt
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Mov Disord 27:272-6. 2012
    ..This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment...
  17. pmc Transgenic mouse model expressing the caspase 6 fragment of mutant huntingtin
    Elaine Waldron-Roby
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neurosci 32:183-93. 2012
    ....
  18. ncbi request reprint Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity
    Wanli W Smith
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 14:3801-11. 2005
    ..This study sheds light into the pathogenesis of alpha-synuclein cellular toxicity in PD and provides a cell model for screening PD therapeutic agents...
  19. ncbi request reprint Parkinson's disease genetic mutations increase cell susceptibility to stress: mutant alpha-synuclein enhances H2O2- and Sin-1-induced cell death
    Haibing Jiang
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neurobiol Aging 28:1709-17. 2007
    ..These results indicate that genetic mutations in alpha-synuclein may increase neuronal vulnerability to cellular stress in aging and PD pathogenesis...
  20. pmc Mutant huntingtin: nuclear translocation and cytotoxicity mediated by GAPDH
    Byoung Il Bae
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 103:3405-9. 2006
    ..Depletion of GAPDH or Siah1 by RNA interference diminishes nuclear translocation of mHtt...
  21. pmc Depressive symptoms in prodromal Huntington's Disease correlate with Stroop-interference related functional connectivity in the ventromedial prefrontal cortex
    Paul G Unschuld
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Psychiatry Res 203:166-74. 2012
    ..These findings suggest that depressive symptoms in prodromal HD subjects may reflect altered functional brain network activity in the context of early HD-related brain alterations...
  22. ncbi request reprint Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington's disease patient lymphoblasts
    Akira Sawa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Neurobiol Dis 20:267-74. 2005
    ..Our findings suggest that caspase cleavage of Htt is cytoplasmic and precedes sorting to specific perinuclear sites followed by nuclear translocation in HD patient tissue...
  23. pmc Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis
    Tamara Ratovitski
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Cell Cycle 11:2006-21. 2012
    ....
  24. pmc Brain metabolite alterations and cognitive dysfunction in early Huntington's disease
    Paul G Unschuld
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Mov Disord 27:895-902. 2012
    ....
  25. pmc Spatiotemporal mapping of brain atrophy in mouse models of Huntington's disease using longitudinal in vivo magnetic resonance imaging
    Manisha Aggarwal
    Division of NMR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuroimage 60:2086-95. 2012
    ..The findings of this report can be used for future testing and comparison of potential therapeutics in mouse models of HD...
  26. pmc The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model
    Qi Peng
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Exp Neurol 210:154-63. 2008
    ..Our findings suggest that a clinical trial of SSRI treatment in order to retard disease progression in human HD may be warranted...
  27. pmc CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity
    Han Seok Ko
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 106:2897-902. 2009
    ..Thus, increasing CHIP E3 ligase activity and blocking HSP90 chaperone activity can prevent the deleterious effects of LRRK2. These findings point to potential treatment options for LRRK2-associated PD...
  28. pmc Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington's disease
    Mali Jiang
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 22:2462-70. 2013
    ..These data highlight consideration of TrkB as a therapeutic target in HD and suggest that small-molecule TrkB agonists that penetrate the brain have high potential to be further tested in clinical trials of HD...
  29. ncbi request reprint A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development
    Atsushi Kamiya
    Department of Psychiatry Neurobiology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, CMSC 8 117, Baltimore, MD 21287, USA
    Nat Cell Biol 7:1167-78. 2005
    ..These results indicate that DISC1 is involved in cerebral cortex development, and suggest that loss of DISC1 function may underlie neurodevelopmental dysfunction in schizophrenia...
  30. ncbi request reprint Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell model
    Wenfei Wang
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2109, USA
    Neurobiol Dis 20:500-8. 2005
    ..We also tested a broad spectrum caspase inhibitor Z-VAD-fmk and previously proposed candidate compounds. This cell model can provide a method to screen potential therapeutic compounds for treating Huntington's disease...
  31. ncbi request reprint Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice
    Gabriele Schilling
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 13:1599-610. 2004
    ..These data suggest that disruption of nuclear processes may account for many of the disease phenotypes displayed in the mouse models generated by expressing mutant N-terminal fragments of htt...
  32. pmc Animal models of gene-environment interactions in schizophrenia
    Yavuz Ayhan
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Behav Brain Res 204:274-81. 2009
    ..We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay...
  33. pmc Identification of novel potentially toxic oligomers formed in vitro from mammalian-derived expanded huntingtin exon-1 protein
    Leslie G Nucifora
    Division of Neurobiology, Department of Psychiatry, Children s Medical Surgical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Biol Chem 287:16017-28. 2012
    ..In addition, these studies demonstrate the fundamental differences in early aggregation events between mutant huntingtin exon-1 and shortstop proteins that may underlie the differences in toxicity...
  34. doi request reprint Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis
    Ana I Seixas
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Ann Neurol 71:245-57. 2012
    ..The aim of this study was to test the possibility that loss of JPH3 expression or expanded amino acid tracts also contribute to HDL2 pathogenesis...
  35. doi request reprint A comparison of huntington disease and huntington disease-like 2 neuropathology
    Dobrila D Rudnicki
    Division of Neurobiology, Department of Psychiatry, John Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Neuropathol Exp Neurol 67:366-74. 2008
    ..Overall, the neuropathologic features of HDL2 and HD are very similar but not identical, suggesting that the pathogenetic mechanisms of the 2 diseases may partially overlap...
  36. pmc Neuropsychological deficits in Huntington's disease gene carriers and correlates of early "conversion"
    Jason Brandt
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    J Neuropsychiatry Clin Neurosci 20:466-72. 2008
    ..People with the Huntington's disease mutation who are carefully examined neurologically and found to be asymptomatic have, at most, very minimal problem-solving impairment, and only if they are within a few years of clinical onset...
  37. ncbi request reprint N-terminal proteolysis of full-length mutant huntingtin in an inducible PC12 cell model of Huntington's disease
    Tamara Ratovitski
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Cell Cycle 6:2970-81. 2007
    ..Further delineation of huntingtin cleavage events may lead to novel therapeutic targets for HD...
  38. ncbi request reprint p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease
    Byoung Il Bae
    Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Neuron 47:29-41. 2005
    ..Genetic deletion of p53 suppresses neurodegeneration in mHtt-Tg flies and neurobehavioral abnormalities of mHtt-Tg mice. Our findings suggest that p53 links nuclear and mitochondrial pathologies characteristic of HD...
  39. pmc Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
    Andrew B West
    Institute for Cell Engineering, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:16842-7. 2005
    ..These results suggest a gain-of-function mechanism for LRRK2-linked disease with a central role for kinase activity in the development of PD...
  40. doi request reprint Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets
    Mali Jiang
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Med 18:153-8. 2012
    ..These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease...
  41. ncbi request reprint PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation
    Mikhail V Pletnikov
    Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurosci Res 58:234-44. 2007
    ..Thus, inducible expression of DISC1 in PC12 cell clones is a valuable in vitro model for further studying the molecular mechanisms likely due to loss of function of DISC1 relevant to the pathogenesis of major mental illnesses...
  42. ncbi request reprint Primate disrupted-in-schizophrenia-1 (DISC1): high divergence of a gene for major mental illnesses in recent evolutionary history
    Lyuda Bord
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurosci Res 56:286-93. 2006
    ....
  43. pmc Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism
    Mali Jiang
    Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neurochem 114:419-29. 2010
    ..Baicalein has potential as a tool to understand the relation between different aggregation species and toxicity, and might be a candidate compound for further validation by using in vivo alpha-syn genetic PD models...
  44. pmc Cysteine proteases bleomycin hydrolase and cathepsin Z mediate N-terminal proteolysis and toxicity of mutant huntingtin
    Tamara Ratovitski
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    J Biol Chem 286:12578-89. 2011
    ..Our findings further validate the cysteine protease family, and BLMH and cathepsin Z in particular, as potential novel targets for HD therapeutics...
  45. ncbi request reprint Regional white matter change in pre-symptomatic Huntington's disease: a diffusion tensor imaging study
    Sarah A J Reading
    Division of Psychiatric Neuroimaging, Department of Psychiatry, The Johns Hopkins University, Phipps 313, Baltimore, MD 21287, USA
    Psychiatry Res 140:55-62. 2005
    ..Our results indicate that, before the onset of manifest HD, there are regional decreases in fractional anisotropy, indicating early white matter disorganization...
  46. doi request reprint Prefrontal executive function associated coupling relates to Huntington's disease stage
    Paul G Unschuld
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland Electronic address
    Cortex 49:2661-73. 2013
    ..Additional longitudinal studies may reveal temporal relationships between impaired task-related premotor-MPFC coupling and other brain changes in HD. ..
  47. ncbi request reprint Huntington's Disease-like 2 (HDL2) in North America and Japan
    Russell L Margolis
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Ann Neurol 56:670-4. 2004
    ..0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype...
  48. pmc A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse
    Naoya Sawamura
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 102:1187-92. 2005
    ..These results suggest that DISC1 may be implicated in psychiatric conditions in other populations than the unique Scottish family...
  49. pmc Longitudinal characterization of brain atrophy of a Huntington's disease mouse model by automated morphological analyses of magnetic resonance images
    Jiangyang Zhang
    Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuroimage 49:2340-51. 2010
    ..This is the first report of longitudinal characterization of brain atrophy in a mouse model of Huntington's disease by using automatic morphological analysis...
  50. pmc Acute kidney injury leads to inflammation and functional changes in the brain
    Manchang Liu
    Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
    J Am Soc Nephrol 19:1360-70. 2008
    ..These data demonstrate that severe ischemic AKI induces inflammation and functional changes in the brain. Targeting these pathways could reduce morbidity and mortality in critically ill patients with severe AKI...
  51. ncbi request reprint Characterization of huntingtin pathologic fragments in human Huntington disease, transgenic mice, and cell models
    Gabriele Schilling
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Neuropathol Exp Neurol 66:313-20. 2007
    ....
  52. ncbi request reprint A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration
    Daniel Goti
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neurosci 24:10266-79. 2004
    ....
  53. pmc Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington's disease patient cells
    Tarja A Juopperi
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Brain 5:17. 2012
    ..The development of experimental systems based on iPSC technology could aid in the identification of molecular lesions and therapeutic treatments...
  54. pmc Diffuse abnormality of low to moderately organized white matter in schizophrenia
    Sarah A J Reading
    Division of Neuroimaging, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Brain Connect 1:511-9. 2011
    ....
  55. pmc trans-(-)-ε-Viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington Disease
    Jinrong Fu
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Biol Chem 287:24460-72. 2012
    ..Our results suggest that increasing mitochondrial SIRT3 might be considered as a new therapeutic approach to counteract HD, as well as other neurodegenerative diseases with similar mechanisms...
  56. doi request reprint Factors contributing to institutionalization in patients with Huntington's disease
    Adam Rosenblatt
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mov Disord 26:1711-6. 2011
    ..This may illustrate the especially debilitating nature of the movement disorder of Huntington's disease in comparison with the other dementias...
  57. pmc A Drosophila model for LRRK2-linked parkinsonism
    Zhaohui Liu
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 105:2693-8. 2008
    ..These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention...
  58. ncbi request reprint Autophagosome-like vacuole formation in Huntington's disease lymphoblasts
    Eiichiro Nagata
    Departments of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
    Neuroreport 15:1325-8. 2004
    ..Our findings provide direct evidence for abnormalities in Huntington's disease tissues outside the brain under basal conditions. Autophagic cellular alterations may be utilized as peripheral markers of Huntington's disease pathology...
  59. ncbi request reprint Functional brain changes in presymptomatic Huntington's disease
    Sarah A J Reading
    Department of Psychiatry, Johns Hopkins University, Baltimore, MD 21287, USA
    Ann Neurol 55:879-83. 2004
    ..In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls...
  60. doi request reprint Huntington disease: pathogenesis, biomarkers, and approaches to experimental therapeutics
    Christopher A Ross
    Professor of Psychiatry, Neurology, Pharmacology and Neuroscience, Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Parkinsonism Relat Disord 15:S135-8. 2009
    ....
  61. doi request reprint Gene-environment interactions in Parkinson's disease
    Christopher A Ross
    Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Parkinsonism Relat Disord 13:S309-15. 2007
    ..None of the single models replicate all the features of PD. Genetic models (possibly including more than one mutation) in combination with toxins or other environmental manipulation may provide better models of PD pathogenesis...
  62. ncbi request reprint Huntington's disease--like 2 is associated with CUG repeat-containing RNA foci
    Dobrila D Rudnicki
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Ann Neurol 61:272-82. 2007
    ..The goal of this study, therefore, was to test the plausibility of an RNA gain-of-function component in the pathogenesis of HDL2...
  63. ncbi request reprint A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure
    Michelle A Poirier
    Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 14:765-74. 2005
    ..We found our data support this model in the htt protein and provide a better understanding of the structural basis of polyQ aggregation in toxicity in HD...
  64. pmc Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease
    Paul G Unschuld
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurosci Lett 514:204-9. 2012
    ..Additional longitudinal studies are necessary to elucidate the temporal relationship between functional alterations and earliest structural brain changes in prodromal-HD...
  65. ncbi request reprint Protein aggregation and neurodegenerative disease
    Christopher A Ross
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Ross Research Building, Room 618, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Med 10:S10-7. 2004
    ..There is now increased understanding of the pathways involved in protein aggregation, and some recent clues have emerged as to the molecular mechanisms of cellular toxicity. These are leading to approaches toward rational therapeutics...
  66. ncbi request reprint Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicity
    Frederick C Nucifora
    Division of Neurobiology, Department of Psychiatry, and The Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Biol Chem 278:13047-55. 2003
    ..These data indicate that truncation of atrophin-1 may alter its ability to shuttle between the nucleus and cytoplasm, leading to abnormal nuclear interactions and cell toxicity...
  67. ncbi request reprint Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formation
    Kah Leong Lim
    Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 25:2002-9. 2005
    ..Our results suggest that parkin is a dual-function ubiquitin ligase and that K63-linked ubiquitination of synphilin-1 by parkin may be involved in the formation of Lewy body inclusions associated with PD...
  68. doi request reprint LRRK2 kinase activity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: suppression by curcumin
    Dejun Yang
    Department of Physiology and Pathophysiology, Xi an Jiaotong University School of Medicine, Xi an, Shaanxi, PR China
    Neurobiol Dis 47:385-92. 2012
    ..These studies also identified curcumin as a LRRK2 kinase inhibitor that may be a useful candidate for LRRK2-linked PD intervention...
  69. ncbi request reprint Huntington's disease: new paths to pathogenesis
    Christopher A Ross
    Department of Psychiatry, 618 Ross Research Building, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Cell 118:4-7. 2004
    ..This suggests an intriguing convergence to previously described pathways implicating neurotrophin transcription in HD pathogenesis...
  70. pmc Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology
    Bagrat Abazyan
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA
    Biol Psychiatry 68:1172-81. 2010
    ..We evaluated interaction between mutant human disrupted-in-schizophrenia 1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders...
  71. ncbi request reprint Neurobiology of schizophrenia
    Christopher A Ross
    Division of Neurobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA
    Neuron 52:139-53. 2006
    ..Understanding these basic pathologic processes may yield novel targets for the development of more effective treatments...
  72. pmc Polyglutamine fibrillogenesis: the pathway unfolds
    Christopher A Ross
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 100:1-3. 2003
  73. ncbi request reprint Environmental, pharmacological, and genetic modulation of the HD phenotype in transgenic mice
    Gabriele Schilling
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 2196, USA
    Exp Neurol 187:137-49. 2004
    ..The positive outcomes achieved by CoQ10 therapy and environmental stimuli point toward two potentially therapeutic approaches that should be readily accessible to HD patients and at-risk family members...
  74. ncbi request reprint The ubiquitin-proteasome pathway in Parkinson's disease and other neurodegenerative diseases
    Christopher A Ross
    Johns Hopkins University School of Medicine, Division of Neurobiology, Department of Psychiatry, Ross Research Building, Room 618, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Trends Cell Biol 14:703-11. 2004
    ..However, the exact molecular connections between these systems and pathogenesis remain uncertain and controversial. In this article, we summarize the state of current knowledge, focusing on important unresolved questions...
  75. doi request reprint Long tandem repeats as a form of genomic copy number variation: structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populations
    Heather A Bruce
    Departments of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Psychiatr Genet 19:64-71. 2009
    ..We therefore carried out a pilot experiment to explore the potential role of long tandem repeats as risk factors in psychiatric disorders...
  76. ncbi request reprint Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders
    Christopher A Ross
    Johns Hopkins University School of Medicine, Department of Psychiatry, Division of Neurobiology, Baltimore, MD 21205, USA
    Neuron 35:819-22. 2002
    ..Recent studies using transgenic mouse and Drosophila models have helped resolve some of these issues and raise hopes for development of therapeutic targets...
  77. ncbi request reprint Opinion: What is the role of protein aggregation in neurodegeneration?
    Christopher A Ross
    Division of Neurobiology, Department of Psychiatry at Johns Hopkins University School of Medicine, CMSC 8 121, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
    Nat Rev Mol Cell Biol 6:891-8. 2005
    ..This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets...
  78. pmc A compact beta model of huntingtin toxicity
    Qi Charles Zhang
    Division of Neurobiology, Department of Psychiatry, Children s Medical Surgical Center, Johns Hopkins University School of Medicine, Baltimore, Mayland 21287, USA
    J Biol Chem 286:8188-96. 2011
    ..These data are consistent with an important role for a compact β structure in mutant huntingtin-induced cell toxicity...
  79. ncbi request reprint Cognitive impairment and psychiatric symptoms in 133 patients with diseases associated with cerebellar degeneration
    Christine M Liszewski
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neuropsychiatry Clin Neurosci 16:109-12. 2004
    ..Psychopathology, including depression, personality change, cognitive impairment, anxiety, and psychosis was noted in 51% of 133 patients...
  80. ncbi request reprint Predictors of neuropathological severity in 100 patients with Huntington's disease
    Adam Rosenblatt
    Department of Psychiatry, Johns Hopkins University School of Medicine, Meyer 2 181, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Ann Neurol 54:488-93. 2003
    ..Motor impairment appears to be a good clinical measure of neuronal cell loss, at least late in the course of HD and therefore may prove useful in observational and treatment studies...
  81. ncbi request reprint Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilization
    Michelle A Poirier
    Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, 615 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    J Biol Chem 277:41032-7. 2002
    ....
  82. ncbi request reprint Diagnosis of Huntington disease
    Russell L Margolis
    Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Clin Chem 49:1726-32. 2003
    ..Huntington disease (HD) is a rare, progressive, and fatal autosomal dominant neurodegenerative disorder, typically of adult onset...
  83. ncbi request reprint Psychopathology in patients with degenerative cerebellar diseases: a comparison to Huntington's disease
    Iracema Leroi
    Program in Cellular and Molecular Medicine, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Am J Psychiatry 159:1306-14. 2002
    ..This study estimated the psychiatric morbidity of patients with degenerative cerebellar diseases...
  84. ncbi request reprint Characterization of CTG/CAG repeats on chromosome 18: a study of bipolar disorder
    Theresa Swift-Scanlan
    George Browne Genetics Laboratory, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21287 7463, USA
    Psychiatr Genet 15:91-9. 2005
    ..These 29 trinucleotide-repeat-containing genes may be involved in functional modulation of their respective proteins, and may be candidates for other diseases or disease mechanisms that map to this region...
  85. pmc Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth
    Yuji Ozeki
    Division of Neurobiology and Department of Psychiatry, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 100:289-94. 2003
    ..As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms...