Akira Sawa

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. ncbi request reprint Mechanisms of neuronal cell death in Huntington's disease
    A Sawa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cytogenet Genome Res 100:287-95. 2003
  2. pmc Following the genes: a framework for animal modeling of psychiatric disorders
    Kevin J Mitchell
    Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland
    BMC Biol 9:76. 2011
  3. ncbi request reprint Genetics. Two genes link two distinct psychoses
    Akira Sawa
    Department of Psychiatry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Science 310:1128-9. 2005
  4. doi request reprint Genetic animal models for schizophrenia: advantages and limitations of genetic manipulation in drosophila, zebrafish, rodents, and primates
    Akira Sawa
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Prog Brain Res 179:3-6. 2009
  5. ncbi request reprint Neuron-glia interactions clarify genetic-environmental links in mental illness
    Akira Sawa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer 2 181, Baltimore, MD 21287, USA
    Trends Neurosci 27:294-7. 2004
  6. ncbi request reprint Anti-/Propsychotic drug signaling via heteromeric GPCRs--a balancing act?
    Mari Kondo
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cell 147:964-5. 2011
  7. pmc GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation
    Nilkantha Sen
    Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuron 63:81-91. 2009
  8. pmc DISC1-dependent switch from progenitor proliferation to migration in the developing cortex
    Koko Ishizuka
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Nature 473:92-6. 2011
  9. 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
  10. pmc Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits
    Minae Niwa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neuron 65:480-9. 2010

Detail Information

Publications79

  1. ncbi request reprint Mechanisms of neuronal cell death in Huntington's disease
    A Sawa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cytogenet Genome Res 100:287-95. 2003
    ..In this article, we will summarize the current understanding on mechanisms of how mutant Htt can elicit cytotoxicity, as well as how the selective sets of neuronal cell death occur in HD brains...
  2. pmc Following the genes: a framework for animal modeling of psychiatric disorders
    Kevin J Mitchell
    Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland
    BMC Biol 9:76. 2011
    ....
  3. ncbi request reprint Genetics. Two genes link two distinct psychoses
    Akira Sawa
    Department of Psychiatry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Science 310:1128-9. 2005
  4. doi request reprint Genetic animal models for schizophrenia: advantages and limitations of genetic manipulation in drosophila, zebrafish, rodents, and primates
    Akira Sawa
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Prog Brain Res 179:3-6. 2009
    ..In addition to mouse models, the potential to use drosophila, zebrafish, and primates is underscored...
  5. ncbi request reprint Neuron-glia interactions clarify genetic-environmental links in mental illness
    Akira Sawa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer 2 181, Baltimore, MD 21287, USA
    Trends Neurosci 27:294-7. 2004
    ..The key role for glial BDV-P implicates neuron-glia interactions in the pathogenesis of psychiatric conditions...
  6. ncbi request reprint Anti-/Propsychotic drug signaling via heteromeric GPCRs--a balancing act?
    Mari Kondo
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cell 147:964-5. 2011
    ....
  7. pmc GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation
    Nilkantha Sen
    Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Neuron 63:81-91. 2009
    ..In intact mice, virally delivered GOSPEL selectively diminishes NMDA neurotoxicity. Thus, GOSPEL may physiologically regulate the viability of neurons and other cells...
  8. pmc DISC1-dependent switch from progenitor proliferation to migration in the developing cortex
    Koko Ishizuka
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Nature 473:92-6. 2011
    ..These data highlight a dual role for DISC1 in corticogenesis and indicate that phosphorylation of this protein at S710 activates a key developmental switch...
  9. 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...
  10. pmc Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits
    Minae Niwa
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neuron 65:480-9. 2010
    ....
  11. pmc Neuroprotection by pharmacologic blockade of the GAPDH death cascade
    Makoto R Hara
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 103:3887-9. 2006
    ..In mice treated with the dopamine neuronal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), low doses of deprenyl prevent binding of GAPDH and Siah1 in the dopamine-enriched corpus striatum...
  12. pmc Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis
    Nilkantha Sen
    Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Nat Cell Biol 10:866-73. 2008
    ..Our findings reveal a pathway in which NO-induced nuclear GAPDH mediates cell death through p300/CBP...
  13. 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...
  14. pmc Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses
    Atsushi Kamiya
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 600 N Wolfe St, Baltimore, MD 21287, USA
    Arch Gen Psychiatry 65:996-1006. 2008
    ..A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ)...
  15. pmc Disrupted-in-Schizophrenia-1 expression is regulated by beta-site amyloid precursor protein cleaving enzyme-1-neuregulin cascade
    Saurav Seshadri
    Departments of Psychiatry, Neuroscience, and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 107:5622-7. 2010
    ..These findings may connect NRG1, ErbBs, Akt, and DISC1 in a common pathway, which may regulate neurodevelopment and contribute to susceptibility to schizophrenia...
  16. 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...
  17. 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
    ....
  18. ncbi request reprint DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1
    Atsushi Kamiya
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Hum Mol Genet 15:3313-23. 2006
    ..We demonstrate that genetic variants of DISC1, proximal to the NDEL1 binding site, affect the interaction between DISC1 and NDEL1...
  19. 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...
  20. pmc Subcortical dopaminergic deficits in a DISC1 mutant model: a study in direct reference to human molecular brain imaging
    Hanna Jaaro-Peled
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Hum Mol Genet 22:1574-80. 2013
    ..We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging...
  21. pmc Protein S-nitrosylation: role for nitric oxide signaling in neuronal death
    Neelam Shahani
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Biochim Biophys Acta 1820:736-42. 2012
    ..In particular, an increasing number of studies have identified important roles for S-nitrosylation in regulating cell death...
  22. pmc Modulation of D-serine levels in brains of mice lacking PICK1
    Takatoshi Hikida
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Biol Psychiatry 63:997-1000. 2008
    ..D-serine is an endogenous coagonist of the N-methyl-D-aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with D-serine metabolism in schizophrenia and bipolar disorder...
  23. 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...
  24. 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...
  25. pmc Working memory deficits in neuronal nitric oxide synthase knockout mice: potential impairments in prefrontal cortex mediated cognitive function
    Sandra P Zoubovsky
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Biochem Biophys Res Commun 408:707-12. 2011
    ..These results suggest that nNOS KO mice are useful tools in studying the role of nNOS signaling in cortical development and prefrontal cortical functioning...
  26. pmc Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models
    Hanna Jaaro-Peled
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Schizophr Bull 36:301-13. 2010
    ..Finally, in comparison with the changes in patients and nongenetic models, we will discuss the anatomical and neuropathological manifestation in genetic models for schizophrenia...
  27. pmc Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1
    Akiko Hayashi-Takagi
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nat Neurosci 13:327-32. 2010
    ..Furthermore, the concept of a signalosome involving disease-associated factors, such as DISC1 and glutamate, may well contribute to the multifactorial and polygenetic characteristics of schizophrenia...
  28. ncbi request reprint S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding
    Makoto R Hara
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Nat Cell Biol 7:665-74. 2005
    ..The NO-S-nitrosylation-GAPDH-Siah1 cascade may represent an important molecular mechanism of cytotoxicity...
  29. doi request reprint Glutathione is a physiologic reservoir of neuronal glutamate
    Minori Koga
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Meyer 4 137, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Biochem Biophys Res Commun 409:596-602. 2011
    ..Increased glutamate levels following inhibition of glutathione synthesis temporally precede later effects upon oxidative stress...
  30. 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...
  31. 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...
  32. doi request reprint Altered MHC class I expression in dorsolateral prefrontal cortex of nonsmoker patients with schizophrenia
    Shin ichi Kano
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurosci Res 71:289-93. 2011
    ..We did not observe SZ-associated changes in C3 mRNA expression. Our exploratory research suggests a potential involvement of MHC class I in SZ and implies that smoking might modulate its expression...
  33. ncbi request reprint GAPDH as a sensor of NO stress
    Makoto R Hara
    Department of Neuroscience, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Biochim Biophys Acta 1762:502-9. 2006
    ..The NO/GAPDH/Siah1 death cascade will contribute to the molecular understanding of a role of GAPDH in neurodegenerative disorders and help to establish novel therapeutic strategies...
  34. pmc Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1
    Hanna Jaaro-Peled
    Department of Psychiatry and Behavioral Neurosciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Trends Neurosci 32:485-95. 2009
    ..We provide an update on the role of these emerging concepts in understanding the complex time course of SZ from early neurodevelopmental disturbances to later onset and suggest ways of testing these in the future...
  35. doi request reprint Synapse-specific contributions in the cortical pathology of schizophrenia
    Saurav Seshadri
    Department of Psychiatry, Johns Hopkins University, Baltimore, MD 21287, USA
    Neurobiol Dis 53:26-35. 2013
    ....
  36. doi request reprint The insula-claustrum region and delusions in schizophrenia
    Nicola G Cascella
    Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Schizophr Res 133:77-81. 2011
    ..We examined the relationship between cerebral gray matter (GM) volume and severity of delusions and hallucinations in adults with schizophrenia...
  37. 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...
  38. doi request reprint Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1 in schizophrenia
    David J Schretlen
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
    Schizophr Res 118:224-31. 2010
    ..In these outpatients with schizophrenia, HSV-1 seropositivity and performance on a cognitive test that is highly sensitive to it co-localize to closely overlapping brain regions...
  39. doi request reprint Gray-matter abnormalities in deficit schizophrenia
    Nicola G Cascella
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Schizophr Res 120:63-70. 2010
    ..Further, the neuroanatomic differences between these two putative subtypes of schizophrenia involve brain regions that appear to be associated with the negative symptoms that define the deficit syndrome of schizophrenia...
  40. ncbi request reprint [Neurodevelopmental disturbance in the pathogenesis of major mental disorders]
    Atsushi Kamiya
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, CMSC 9 120, Baltimore MD 21287, USA
    Brain Nerve 60:445-52. 2008
    ..In this review, we will summarize the updates of schizophrenia and autism research, with an emphasis on neurodevelopmental disturbances...
  41. doi request reprint Negative symptoms of schizophrenia correlate with impairment on the University of Pennsylvania smell identification test
    Koko Ishizuka
    Department of Psychiatry, Johns Hopkins University School of Medicine, United States
    Neurosci Res 66:106-10. 2010
    ..Our study further reinforces a relation between olfactory identification deficit and negative symptoms in SZ and suggests that smell identification could be a candidate endophenotype relevant to negative symptoms of SZ...
  42. pmc Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans
    Takatoshi Hikida
    Department of Psychiatry and Behavioral Sciences, Graduate Program in Cellular and Molecular Medicine, and Division of Neurobiology, The Johns Hopkins University, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 104:14501-6. 2007
    ..DN-DISC1 mice also display several behavioral abnormalities, including hyperactivity, disturbance in sensorimotor gating and olfactory-associated behavior, and an anhedonia/depression-like deficit...
  43. ncbi request reprint Differential expression of disrupted-in-schizophrenia (DISC1) in bipolar disorder
    Kazuhisa Maeda
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Biol Psychiatry 60:929-35. 2006
    ..Association of DISC1 with schizophrenia has been reported in several ethnic groups, and now recently with mood disorder...
  44. doi request reprint Diabetes is associated with lower global cognitive function in schizophrenia
    Yoichiro Takayanagi
    Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
    Schizophr Res 142:183-7. 2012
    ..We addressed these questions by re-assessing the cognitive dataset from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study...
  45. pmc Pharmacokinetics of oral D-serine in D-amino acid oxidase knockout mice
    Rana Rais
    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Drug Metab Dispos 40:2067-73. 2012
    ..Thus, a potent DAAO inhibitor with a longer half-life should be capable of maintaining high plasma D-serine levels over a sustained period of time and might have therapeutic implications for the treatment of schizophrenia...
  46. pmc In utero electroporation as a tool for genetic manipulation in vivo to study psychiatric disorders: from genes to circuits and behaviors
    Yu Taniguchi
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Neuroscientist 18:169-79. 2012
    ....
  47. pmc Human nasal olfactory epithelium as a dynamic marker for CNS therapy development
    Rita Sattler
    Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA
    Exp Neurol 232:203-11. 2011
    ..Therefore, this biomarker approach may provide a reliable evaluation of CNS glial-directed therapies and hopefully improve throughput for nervous system drug discovery...
  48. 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...
  49. 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...
  50. 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...
  51. ncbi request reprint DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex
    Brian Kirkpatrick
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    J Comp Neurol 497:436-50. 2006
    ..These anatomical localization data suggest that DISC1 participates in synaptic activity and microtubule function, and are consistent with the limited data on its adult function...
  52. ncbi request reprint Neurodevelopmental involvement in schizophrenia: the olfactory epithelium as an alternative model for research
    Nicola G Cascella
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    J Neurochem 102:587-94. 2007
    ..We agree with the proposal that the olfactory epithelium, in which neurodevelopment continues throughout life, might represent an alternative model for understanding the pathophysiology of the disorder...
  53. 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...
  54. pmc Better understanding of mechanisms of schizophrenia and bipolar disorder: from human gene expression profiles to mouse models
    Chi Ying Lin
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Neurobiol Dis 45:48-56. 2012
    ..We also point out that models in which the metabolic genes are modified are obviously untested from mental illness viewpoints, suggesting the potential to re-address these models with behavioral assays and neurochemical assessments...
  55. doi request reprint Nitric oxide signaling and nitrosative stress in neurons: role for S-nitrosylation
    Neelam Shahani
    Department of Psychiatry, Johns Hopkins University School of Medicine, 600N Wolfe St, Baltimore, MD 21287, USA
    Antioxid Redox Signal 14:1493-504. 2011
    ..In this review, these molecular mechanisms, especially those in the central nervous system and neurodegenerative disorders, are described...
  56. pmc The diverse functions of GAPDH: views from different subcellular compartments
    Carlos Tristan
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Cell Signal 23:317-23. 2011
    ..GAPDH is also involved in various diseases, especially neurodegenerative disorders and cancers. Therapeutic strategies to these conditions based on molecular understanding of GAPDH are discussed...
  57. pmc Alternatively spliced neuronal nitric oxide synthase mediates penile erection
    K Joseph Hurt
    Department of Urology, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 103:3440-3. 2006
    ..Thus, alternatively spliced forms of nNOS are major mediators of penile erection and so may be targets for therapeutic intervention...
  58. pmc Schizophrenia: neural mechanisms for novel therapies
    Akira Sawa
    Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
    Mol Med 9:3-9. 2003
    ..The search for genes linked to schizophrenia has revealed several leads that may permit development of novel therapeutic agents. Promising genes include disrupted-in-schizophrenia-1, dysbindin, and neuregulin...
  59. ncbi request reprint A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions
    Koko Ishizuka
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Biol Psychiatry 59:1189-97. 2006
    ..Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed...
  60. pmc Mouse models of gene-environment interactions in schizophrenia
    Geetha Kannan
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Neurobiol Dis 57:5-11. 2013
    ....
  61. doi request reprint Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: utility and limitation of the surrogate tissues in research for brain disorders
    Yasue Horiuchi
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Neurosci Res 77:247-50. 2013
    ....
  62. doi request reprint Relationships between serum leptin level and severity of positive symptoms in schizophrenia
    Yoichiro Takayanagi
    Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
    Neurosci Res 77:97-101. 2013
    ..There was no correlation between leptin levels and negative symptoms or neurocognition. Our data suggest a role of leptin in SZ positive symptoms. ..
  63. doi request reprint Disturbed synaptic connectivity in schizophrenia: convergence of genetic risk factors during neurodevelopment
    Akiko Hayashi-Takagi
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
    Brain Res Bull 83:140-6. 2010
    ..These genetic risk factors contribute to the process possibly in a synergistic manner. The notion of signal pathways involving more than one genetic factor is in accord with the multifactorial nature of schizophrenia...
  64. pmc Schizophrenia and epilepsy: is there a shared susceptibility?
    Nicola G Cascella
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Neurosci Res 63:227-35. 2009
    ....
  65. pmc Glucocorticoid-induced loss of DNA methylation in non-neuronal cells and potential involvement of DNMT1 in epigenetic regulation of Fkbp5
    Xiaoju Yang
    Department of Medicine, Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Biochem Biophys Res Commun 420:570-5. 2012
    ..Taken together, we provide evidence that these glucocorticoid-induced epigenetic alterations have a broader validity in non-neuronal cells and that they may involve the DNA methylation machinery...
  66. ncbi request reprint Schizophrenia: diverse approaches to a complex disease
    Akira Sawa
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 296:692-5. 2002
    ..Here, we provide a brief overview of the parallel approaches being used to identify the molecular causes of schizophrenia and discuss possible directions for future research...
  67. 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...
  68. ncbi request reprint How has DISC1 enabled drug discovery?
    Qi Wang
    Discovery Neuroscience, Wyeth Research, Princeton, NJ, USA
    Mol Cell Neurosci 37:187-95. 2008
    ..Thus, DISC1 may have the potential to not only point us in the direction of novel drug targets but also provide more relevant animal models for compound testing...
  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 Identification of functional polymorphisms in the promoter region of the human PICK1 gene and their association with methamphetamine psychosis
    Daisuke Matsuzawa
    Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
    Am J Psychiatry 164:1105-14. 2007
    ..Based on the interaction of PICK1 with dopamine transporter, it is of particular interest to investigate the association between the PICK1 gene and methamphetamine abusers...
  71. ncbi request reprint Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses
    Naoya Sawamura
    Consolidated Research Institute for Advanced Science and Medical Care ASMeW, Waseda University, 513 Wasedatsurumaki cho, Shinjuku ku, Tokyo 162 0041, Japan
    Ann N Y Acad Sci 1086:126-33. 2006
    ..These results support involvement of DISC1 in the pathophysiology of major mental conditions, including schizophrenia, in several mechanisms...
  72. ncbi request reprint [DISC1 and schizophrenia]
    Yuji Ozeki
    Department of Psychiatry, Shiga University of Medical Science, Setatsukinowacho, Otsu, 520 2192 Japan
    Nihon Shinkei Seishin Yakurigaku Zasshi 24:87-91. 2004
    ..This concept fits with many historical observations found for schizophrenia in association with neurodevelopmental abnormalities. DISC1 may become one of the key molecules in studying the pathogenesis of schizophrenia...
  73. ncbi request reprint Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs
    Barbara K Lipska
    Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Hum Mol Genet 15:1245-58. 2006
    ..Although, many other DISC1 binding partners still need to be investigated, these data implicate genetically linked abnormalities in the DISC1 molecular pathway in the pathophysiology of schizophrenia...
  74. ncbi request reprint Association study of the DISC1/TRAX locus with schizophrenia in a Japanese population
    Xuan Zhang
    Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo, Tokyo, 113 8655 Japan
    Schizophr Res 79:175-80. 2005
    ..Haplotype analysis did not support the association between the patients and controls. The present study suggests that the DISC1/TRAX locus may not have a major role in Japanese schizophrenia...
  75. pmc Elucidating the relationship between DISC1, NDEL1 and NDE1 and the risk for schizophrenia: evidence of epistasis and competitive binding
    Katherine E Burdick
    Department of Psychiatry Research, The Zucker Hillside Hospital, North Shore Long Island Jewish Health System, Glen Oaks, NY 11004, USA
    Hum Mol Genet 17:2462-73. 2008
    ..These data suggest that NDEL1 significantly influences risk for SZ via an interaction with DISC1. We propose a model where NDEL1 and NDE1 compete for binding with DISC1...
  76. ncbi request reprint Postsynaptic density: a key convergent site for schizophrenia susceptibility factors and possible target for drug development
    Ryota Hashimoto
    The Osaka Hamamatsu Joint Research Center for Child Mental Development, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Drugs Today (Barc) 43:645-54. 2007
    ..PSD may be a promising target for novel classes of drugs to treat schizophrenia...
  77. pmc Elucidating the pathogenesis of schizophrenia
    Akira Sawa
    BMJ 327:632-3. 2003
  78. ncbi request reprint Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling
    Ryota Hashimoto
    Osaka Hamamatsu Joint Research Center for Child Mental Development, Osaka University Graduate School of Medicine, D3, 2 2 Yamadaoka, 4 1 1 Suita, Osaka 565 0871, Japan
    Hum Mol Genet 15:3024-33. 2006
    ..A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD...
  79. ncbi request reprint Causality of stem cell based neurogenesis and depression--to be or not to be, is that the question?
    Robert E Feldmann
    Department of Physiology and Pathophysiology, Division of Systems Physiology, University of Heidelberg, Im Neuenheimer Feld 326, D 69120 Heidelberg, Germany
    J Psychiatr Res 41:713-23. 2007
    ..Without their reliable answering, the fascinating notion of a neurogenic basis for depression will remain to be greatly speculative...

Research Grants8

  1. DISC-1 and its interacting proteins in schizophrenia
    Akira Sawa; Fiscal Year: 2007
    ..They will provide information to understand the pathogenesis of major mental illnesses in the Scottish family, and they may provide insight into some of the mechanisms that underlie SZ and major mental illnesses. ..
  2. Nuclear pathway of DISC1 in major mental illnesses: biochemistry and cell biology
    Akira Sawa; Fiscal Year: 2010
    ....