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| Christopher RossSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Pathogenesis of neurodegenerative diseases associated with expanded glutamine repeats: new answers, new questionsC 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...- The ubiquitin-proteasome pathway in Parkinson's disease and other neurodegenerative diseasesChristopher 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... 
Gene-environment interactions in Parkinson's diseaseChristopher 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...- Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disordersChristopher 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... - Protein aggregation and neurodegenerative diseaseChristopher 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... - Huntington disease: pathogenesis, biomarkers, and approaches to experimental therapeuticsChristopher 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.... - 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... - Neurobiology of schizophreniaChristopher 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... 
Polyglutamine pathogenesisC 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...- Polyglutamine fibrillogenesis: the pathway unfoldsChristopher 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 - A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentrationDaniel Goti
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
J Neurosci 24:10266-79. 2004.... - Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtinHaibing 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... - ATF3 plays a protective role against toxicity by N-terminal fragment of mutant huntingtin in stable PC12 cell lineYideng 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... - Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtinYuji 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... - Animal models of gene-environment interactions in schizophreniaYavuz 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... - The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse modelQi 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... - A comparison of huntington disease and huntington disease-like 2 neuropathologyDobrila 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... - Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic miceGabriele 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... - Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell modelWenfei 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... - 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 miceVeronica 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... - p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's diseaseByoung 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... - Huntington's disease: new paths to pathogenesisChristopher 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... - Parkin mediates nonclassical, proteasomal-independent ubiquitination of synphilin-1: implications for Lewy body formationKah 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... - Characterization of huntingtin pathologic fragments in human Huntington disease, transgenic mice, and cell modelsGabriele Schilling
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Neuropathol Exp Neurol 66:313-20. 2007.... - Huntington's disease: from molecular pathogenesis to clinical treatmentChristopher 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... - Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicityFrederick 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... - Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cellsTamara 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... - A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structureMichelle 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... - N-terminal proteolysis of full-length mutant huntingtin in an inducible PC12 cell model of Huntington's diseaseTamara 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... - Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's diseaseWenzhen 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... - CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approachesDouglas 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... - Challenges assessing clinical endpoints in early Huntington diseaseJane 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... - Kinase activity of mutant LRRK2 mediates neuronal toxicityWanli 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... - A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex developmentAtsushi 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... - Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington's disease patient lymphoblastsAkira 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... - Mutant huntingtin: nuclear translocation and cytotoxicity mediated by GAPDHByoung 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... - Tiagabine is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's diseaseNaoki 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... - Longitudinal characterization of brain atrophy of a Huntington's disease mouse model by automated morphological analyses of magnetic resonance imagesJiangyang 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... - Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse modelWanli 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... - Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilizationMichelle 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.... - Autophagosome-like vacuole formation in Huntington's disease lymphoblastsEiichiro 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... - Environmental, pharmacological, and genetic modulation of the HD phenotype in transgenic miceGabriele 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... - 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... - Diagnosis of Huntington diseaseRussell 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... - CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicityHan 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... - Parkinson's disease genetic mutations increase cell susceptibility to stress: mutant alpha-synuclein enhances H2O2- and Sin-1-induced cell deathHaibing 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... - Acute kidney injury leads to inflammation and functional changes in the brainManchang 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... - Long tandem repeats as a form of genomic copy number variation: structure and length polymorphism of a chromosome 5p repeat in control and schizophrenia populationsHeather 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... - Huntington's disease--like 2 is associated with CUG repeat-containing RNA fociDobrila 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... - PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiationMikhail 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... - Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar ParkinsonismMali 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... - A Drosophila model for LRRK2-linked parkinsonismZhaohui 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... - Preparing for preventive clinical trials: the Predict-HD studyJane 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... - Psychopathology in patients with degenerative cerebellar diseases: a comparison to Huntington's diseaseIracema 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..These results also support previous findings that the cerebellum may have a role in modulating emotion and cognition... - Primate disrupted-in-schizophrenia-1 (DISC1): high divergence of a gene for major mental illnesses in recent evolutionary historyLyuda Bord
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Neurosci Res 56:286-93. 2006.... - Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicityWanli 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... - Huntington's Disease-like 2 (HDL2) in North America and JapanRussell 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... - Predictors of neuropathological severity in 100 patients with Huntington's diseaseAdam 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... - Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cellsWanli 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... - A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuseNaoya 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... - Functional brain changes in presymptomatic Huntington's diseaseSarah 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... - Characterization of CTG/CAG repeats on chromosome 18: a study of bipolar disorderTheresa 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... - "Frontal" behaviors before the diagnosis of Huntington's disease and their relationship to markers of disease progression: evidence of early lack of awarenessKevin 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... - Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degenerationWanli 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.... - Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowthYuji 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... - 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 diseaseBruce 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... - Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's diseaseFrank P Marx
Department of Neurology, Laboratory of Neurodegeneration, University of Tubingen, Tubingen, Germany
Hum Mol Genet 12:1223-31. 2003.... - Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding proteinHaibing 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... - Inducible PC12 cell model of Huntington's disease shows toxicity and decreased histone acetylationShuichi 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... - Transglutaminase cross-links in intranuclear inclusions in Huntington diseaseGina 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... - Polyglutamine repeat length-dependent proteolysis of huntingtinBanghua Sun
Amgen Inc, Thousand Oaks, California 91320, USA
Neurobiol Dis 11:111-22. 2002.... - Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effectsRuth 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... - 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 lengthLuis Pereira de Almeida
Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, 1011 Lausanne, Switzerland
J Neurosci 22:3473-83. 2002.... - Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicityBirgit 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... - The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtinHélène 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... - Calmodulin regulates transglutaminase 2 cross-linking of huntingtinGina 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... - Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behaviorEdmond 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... - Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's diseaseEsti 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... - Polyglutamine expansion of huntingtin impairs its nuclear exportJonathan 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... - FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's diseaseKunlin 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... - Mutant huntingtin protein: a substrate for transglutaminase 1, 2, and 3Gina 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... - Transcription meets metabolism in neurodegenerationChristopher A Ross
Nat Med 12:1239-41. 2006 - Immunocytochemical localization of synphilin-1, an alpha-synuclein-associated protein, in neurodegenerative disordersKoichi 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... - 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... - Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16Luc 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... - Beyond disgust: impaired recognition of negative emotions prior to diagnosis in Huntington's diseaseShannon 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... 
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....- Bioactivity profiling with parallel mass spectrometry reveals an assemblage of green tea metabolites affording protection against human huntingtin and alpha-synuclein toxicityRussell 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....
Research Grants
- Transgenic Models of Huntington's DiseaseChristopher Ross; Fiscal Year: 2006..The new mouse model will be useful for studying pathogenic features of HD, and for testing experimental therapeutic interventions. ..
- Neurodegeneration and Polyglutamine Toxicity DRPLAChristopher Ross; Fiscal Year: 2007..Proteolytic cleavage would be an especially good target for therapeutic interventions. ..
- INTERDISCIPLINARY TRAINING IN PSYCHIATRY & NEUROSCIENCEChristopher 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. ..
- LRRK2 and Parkinson's Disease Cell BiologyChristopher 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. ..
- PREQUEL Study In PRE-manifest HD of CoQ10/UbiquinonE Leading to Preventive TrialsChristopher Ross; Fiscal Year: 2009....
- LRRK2 and Parkinson's Disease Cell BiologyChristopher 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. ..
- TRANSGENIC MODELS OF HUNTINGTONS DISEASEChristopher Ross; Fiscal Year: 2002..These experiments will clarify the pathogenesis of HD and provide models for future studies of experimental therapeutics. ..
- NEURODEGENERATION AND GENES WITH TRIPLET REPEATSChristopher 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. ..
- PREQUEL Study In PRE-manifest HD of CoQ10/UbiquinonE Leading to Preventive TrialsChristopher A Ross; Fiscal Year: 2010....