Christopher Ross

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. 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
  2. ncbi request reprint Pathogenesis of neurodegenerative diseases associated with expanded glutamine repeats: new answers, new questions
    C A Ross
    Johns Hopkins University, School of Medicine, Department of Psychiatry, Baltimore, Maryland 21205 2196, USA
    Prog Brain Res 117:397-419. 1998
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

Detail Information

Publications89

  1. 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...
  2. ncbi request reprint Pathogenesis of neurodegenerative diseases associated with expanded glutamine repeats: new answers, new questions
    C A Ross
    Johns Hopkins University, School of Medicine, Department of Psychiatry, Baltimore, Maryland 21205 2196, USA
    Prog Brain Res 117:397-419. 1998
    ..As the investigation of the link between these inclusions and cell dysfunction and death continues, it is possible that new avenues for therapeutic intervention will emerge...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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
  9. 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
    ....
  10. 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...
  11. pmc Polyglutamine pathogenesis
    C A Ross
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Philos Trans R Soc Lond B Biol Sci 354:1005-11. 1999
    ..Taken together, these data lead towards a model whereby proteolytic processing, nuclear localization and protein aggregation all contribute to pathogenesis...
  12. 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
    ....
  13. 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...
  14. 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...
  15. 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...
  16. 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...
  17. 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...
  18. 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...
  19. 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...
  20. 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...
  21. 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...
  22. 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...
  23. 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
    ....
  24. 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...
  25. 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...
  26. 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...
  27. 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...
  28. 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...
  29. 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...
  30. 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...
  31. 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...
  32. pmc CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches
    Douglas R Langbehn
    Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 1000, USA
    Am J Med Genet B Neuropsychiatr Genet 153:397-408. 2010
    ..The Langbehn et al. model appears accurate enough to have substantial utility in various research contexts. We also emphasize remaining caveats, many of which are relevant for any direct application to genetic counseling...
  33. pmc Challenges assessing clinical endpoints in early Huntington disease
    Jane S Paulsen
    Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242 1000, USA
    Mov Disord 25:2595-603. 2010
    ..We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life function...
  34. 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...
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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
    ....
  44. 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...
  45. 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...
  46. 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...
  47. 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...
  48. 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...
  49. 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. 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...
  56. 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...
  57. 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
    ....
  58. 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...
  59. 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...
  60. ncbi request reprint Preparing for preventive clinical trials: the Predict-HD study
    Jane S Paulsen
    Department of Psychiatry, University of Iowa, Iowa City 52242 1000, USA
    Arch Neurol 63:883-90. 2006
    ..The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown...
  61. pmc "Frontal" behaviors before the diagnosis of Huntington's disease and their relationship to markers of disease progression: evidence of early lack of awareness
    Kevin Duff
    Department of Psychiatry, University of Iowa College of Medicine, Iowa City, USA
    J Neuropsychiatry Clin Neurosci 22:196-207. 2010
    ..Participant/companion discrepancies, especially closest to Huntington's disease diagnosis, might suggest early lack of awareness in these individuals...
  62. 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...
  63. 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...
  64. 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...
  65. 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
    ....
  66. 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...
  67. ncbi request reprint Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease
    Frank P Marx
    Department of Neurology, Laboratory of Neurodegeneration, University of Tubingen, Tubingen, Germany
    Hum Mol Genet 12:1223-31. 2003
    ....
  68. ncbi request reprint Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding protein
    Haibing Jiang
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Hum Mol Genet 12:1-12. 2003
    ..Thus, selected substrates may be directed to the ubiquitin/proteasome-dependent protein degradation pathway in response to polyQ-expanded htt within the nucleus...
  69. ncbi request reprint Inducible PC12 cell model of Huntington's disease shows toxicity and decreased histone acetylation
    Shuichi Igarashi
    Department of Neuroscience, Brain Research Institute, Niigata University, I Asahimachi, Niigata 951 8585, Japan
    Neuroreport 14:565-8. 2003
    ..These data suggest that altered chromatin modification via reduction in coactivator activity may cause neuronal transcriptional dysregulation and contribute to cellular toxicity...
  70. ncbi request reprint Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior
    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
    Hum Mol Genet 11:945-59. 2002
    ..HAP-1 is particularly enriched in the hypothalamus, which is well documented to regulate feeding behavior. Our results demonstrate that HAP-1 plays an essential role in regulating postnatal feeding...
  71. ncbi request reprint Transglutaminase cross-links in intranuclear inclusions in Huntington disease
    Gina M Zainelli
    Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois 60153, USA
    J Neuropathol Exp Neurol 62:14-24. 2003
    ..Based on these and other studies, modulation of transglutaminase activity could be explored as a treatment for HD...
  72. ncbi request reprint Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length
    Luis Pereira de Almeida
    Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, 1011 Lausanne, Switzerland
    J Neurosci 22:3473-83. 2002
    ....
  73. ncbi request reprint Polyglutamine repeat length-dependent proteolysis of huntingtin
    Banghua Sun
    Amgen Inc, Thousand Oaks, California 91320, USA
    Neurobiol Dis 11:111-22. 2002
    ....
  74. ncbi request reprint Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects
    Ruth Luthi-Carter
    Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital, Charlestown, MA 02129 4404, USA
    Hum Mol Genet 11:1927-37. 2002
    ..These results demonstrate that some of the gene expression effects of expanded polyglutamine proteins occur independently of protein context...
  75. ncbi request reprint 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
    ..Dissection of phosphorylation modifications in Htt may provide clues to Huntington disease pathogenesis and targets for therapeutic development...
  76. ncbi request reprint The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin
    Hélène Rangone
    UMR 146 CNRS Institut Curie, Bldg 110, Centre Universitaire, 91405 Orsay Cedex, France
    Eur J Neurosci 19:273-9. 2004
    ..Collectively, our results strongly suggest the involvement of SGK in HD and further imply that IGF-1 downstream signalling is a key transduction pathway that regulates the toxicity of huntingtin...
  77. ncbi request reprint Calmodulin regulates transglutaminase 2 cross-linking of huntingtin
    Gina M Zainelli
    Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois 60153, USA
    J Neurosci 24:1954-61. 2004
    ..Inhibiting the interaction of calmodulin with transglutaminase and huntingtin protein could decrease cross-linking and diminish huntingtin aggregate formation in the HD brain...
  78. ncbi request reprint Polyglutamine expansion of huntingtin impairs its nuclear export
    Jonathan Cornett
    Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
    Nat Genet 37:198-204. 2005
    ..These results suggest that Tpr has a role in the nuclear export of N-terminal htt and that polyQ expansion reduces this nuclear export to cause the nuclear accumulation of htt...
  79. pmc Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease
    Esti Liani
    Department of Pharmacology, The B Rappaport Institute of Medical Research, Technion Israel Institute of Technology, Haifa 31096, Israel
    Proc Natl Acad Sci U S A 101:5500-5. 2004
    ..In vitro experiments show that SIAH-2 monoubiquitylates alpha-synuclein. Further evidence that SIAH proteins may play a role in inclusion formation comes from the demonstration of SIAH immunoreactivity in Lewy bodies of PD patients...
  80. ncbi request reprint Mutant huntingtin protein: a substrate for transglutaminase 1, 2, and 3
    Gina M Zainelli
    Department of Pharmacology, 2160 S First Avenue, Maywood, IL 60153, USA
    J Neuropathol Exp Neurol 64:58-65. 2005
    ..These data suggest that transglutaminase 1, 2, and 3 could be involved in cross-linking of huntingtin into intranuclear inclusions in HD and that inhibiting transglutaminase should be explored as a potential treatment strategy for HD...
  81. pmc FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's disease
    Kunlin Jin
    The Buck Institute for Age Research, Novato, CA 94945, USA
    Proc Natl Acad Sci U S A 102:18189-94. 2005
    ..We conclude that FGF-2 improves neurological deficits and longevity in a transgenic mouse model of HD, and that its neuroprotective and neuroproliferative effects may contribute to this improvement...
  82. ncbi request reprint Transcription meets metabolism in neurodegeneration
    Christopher A Ross
    Nat Med 12:1239-41. 2006
  83. ncbi request reprint Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease
    Bruce G Jenkins
    MGH NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurochem 95:553-62. 2005
    ..Our results indicate profound metabolic defects that are strongly affected by CAG repeat length, as well as gene expression levels and protein context...
  84. pmc Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study
    Jian Liang Li
    Department of Neurology, Boston University School of Medicine, Boston, MA, USA
    BMC Med Genet 7:71. 2006
    ....
  85. ncbi request reprint Beyond disgust: impaired recognition of negative emotions prior to diagnosis in Huntington's disease
    Shannon A Johnson
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
    Brain 130:1732-44. 2007
    ..In contrast to previous results, we found no evidence of relative impairments in recognizing disgust or fear, and no evidence to support a link between the striatum and disgust recognition...
  86. ncbi request reprint Bioactivity profiling with parallel mass spectrometry reveals an assemblage of green tea metabolites affording protection against human huntingtin and alpha-synuclein toxicity
    Russell B Williams
    Natural Products Discovery Group, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, USA
    J Agric Food Chem 55:9450-6. 2007
    ....
  87. pmc Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16
    Luc Djousse
    Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA
    Neurogenetics 5:109-14. 2004
    ..Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker...
  88. pmc A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study
    Jian 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...
  89. ncbi request reprint Immunocytochemical localization of synphilin-1, an alpha-synuclein-associated protein, in neurodegenerative disorders
    Koichi Wakabayashi
    Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu cho, Hirosaki 036 8562, Japan
    Acta Neuropathol 103:209-14. 2002
    ..These findings suggest that abnormal accumulation of synphilin-1 is specific for brain lesions in which alpha-synuclein is a major component...

Research Grants31

  1. Transgenic Models of Huntington's Disease
    Christopher Ross; Fiscal Year: 2006
    ..The new mouse model will be useful for studying pathogenic features of HD, and for testing experimental therapeutic interventions. ..
  2. Neurodegeneration and Polyglutamine Toxicity DRPLA
    Christopher Ross; Fiscal Year: 2007
    ..Proteolytic cleavage would be an especially good target for therapeutic interventions. ..
  3. INTERDISCIPLINARY TRAINING IN PSYCHIATRY & NEUROSCIENCE
    Christopher Ross; Fiscal Year: 2007
    ..The goal of the program is to prepare future academic researchers to undertake a career in the investigation of the biology of mental disorders. ..
  4. LRRK2 and Parkinson's Disease Cell Biology
    Christopher Ross; Fiscal Year: 2007
    ..These studies will help define the role of LRRK2 and its interacting proteins in cellular pathogenesis related to PD, and potentially identify targets for future therapeutic interventions. ..
  5. PREQUEL Study In PRE-manifest HD of CoQ10/UbiquinonE Leading to Preventive Trials
    Christopher Ross; Fiscal Year: 2009
    ....
  6. LRRK2 and Parkinson's Disease Cell Biology
    Christopher A Ross; Fiscal Year: 2010
    ..These studies will help define the role of LRRK2 and its interacting proteins in cellular pathogenesis related to PD, and potentially identify targets for future therapeutic interventions. ..
  7. TRANSGENIC MODELS OF HUNTINGTONS DISEASE
    Christopher Ross; Fiscal Year: 2002
    ..These experiments will clarify the pathogenesis of HD and provide models for future studies of experimental therapeutics. ..
  8. NEURODEGENERATION AND GENES WITH TRIPLET REPEATS
    Christopher Ross; Fiscal Year: 2002
    ..These studies will be carried out in parallel with ongoing studies in the PI's lab of the HD gene product. Together these studies should shed light on genes involved in these neurodegenerative disorders. ..
  9. PREQUEL Study In PRE-manifest HD of CoQ10/UbiquinonE Leading to Preventive Trials
    Christopher A Ross; Fiscal Year: 2010
    ....