Takashi Nonaka

Summary

Affiliation: Tokyo Institute of Psychiatry
Country: Japan

Publications

  1. doi Phosphorylated and ubiquitinated TDP-43 pathological inclusions in ALS and FTLD-U are recapitulated in SH-SY5Y cells
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya ku 156 8585, Tokyo, Japan
    FEBS Lett 583:394-400. 2009
  2. doi Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Hum Mol Genet 18:3353-64. 2009
  3. pmc A cellular model to monitor proteasome dysfunction by alpha-synuclein
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585
    Biochemistry 48:8014-22. 2009
  4. ncbi Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages
    Takashi Nonaka
    Division of Cell Biology and Biochemistry, Department of Basic Medical Sciences, The Institute of Medical Science, University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Microbiology 149:2513-27. 2003
  5. doi Molecular dissection of TDP-43 proteinopathies
    Masato Hasegawa
    Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2 1 6 Kamikitazawa, Setagaya Ku, Tokyo, 156 8506, Japan
    J Mol Neurosci 45:480-5. 2011
  6. pmc Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Kamikitazawa, Setagaya Ku, Tokyo, Japan
    Ann Neurol 64:60-70. 2008
  7. ncbi [Significance of the TDP-43 deposition in FTLD-U and ALS]
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research
    Rinsho Shinkeigaku 48:994-7. 2008
  8. doi Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS
    Yuki Inukai
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    FEBS Lett 582:2899-904. 2008
  9. doi Identification of casein kinase-1 phosphorylation sites on TDP-43
    Fuyuki Kametani
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Biochem Biophys Res Commun 382:405-9. 2009
  10. ncbi TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya Ku, Tokyo 156 8585, Japan
    Biochem Biophys Res Commun 351:602-11. 2006

Collaborators

Detail Information

Publications41

  1. doi Phosphorylated and ubiquitinated TDP-43 pathological inclusions in ALS and FTLD-U are recapitulated in SH-SY5Y cells
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya ku 156 8585, Tokyo, Japan
    FEBS Lett 583:394-400. 2009
    ..Our results suggest that intracellular localization of TDP-43 and proteasomal function may be involved in inclusion formation and neurodegeneration in TDP-43 proteinopathies...
  2. doi Truncation and pathogenic mutations facilitate the formation of intracellular aggregates of TDP-43
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Hum Mol Genet 18:3353-64. 2009
    ....
  3. pmc A cellular model to monitor proteasome dysfunction by alpha-synuclein
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585
    Biochemistry 48:8014-22. 2009
    ..The cellular model expressing both GFP-CL1 and alpha-synuclein may be a useful tool to screen compounds protecting neurons from alpha-synuclein-mediated proteasome dysfunction...
  4. ncbi Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages
    Takashi Nonaka
    Division of Cell Biology and Biochemistry, Department of Basic Medical Sciences, The Institute of Medical Science, University of Tokyo, 4 6 1, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Microbiology 149:2513-27. 2003
    ..Thus, Shigella can induce rapid necrosis of macrophage-like cells in a virulence-related manner by forming pores in the host cell membrane while some cells can be killed through apoptosis in a virulence-independent fashion...
  5. doi Molecular dissection of TDP-43 proteinopathies
    Masato Hasegawa
    Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2 1 6 Kamikitazawa, Setagaya Ku, Tokyo, 156 8506, Japan
    J Mol Neurosci 45:480-5. 2011
    ....
  6. pmc Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Kamikitazawa, Setagaya Ku, Tokyo, Japan
    Ann Neurol 64:60-70. 2008
    ..The aim of this study was to identify the phosphorylation sites and responsible kinases, and to clarify the pathological significance of phosphorylation of TDP-43...
  7. ncbi [Significance of the TDP-43 deposition in FTLD-U and ALS]
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research
    Rinsho Shinkeigaku 48:994-7. 2008
    ..These findings together with recent discovery of mutations in the TDP-43 gene in ALS strongly suggest that TDP-43 is the..
  8. doi Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS
    Yuki Inukai
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    FEBS Lett 582:2899-904. 2008
    ..Analysis of postmortem changes of TDP-43 revealed that the amounts of Sarkosyl-insoluble, urea-soluble full-length TDP-43 and a 35kDa N-terminal fragment increased time-dependently...
  9. doi Identification of casein kinase-1 phosphorylation sites on TDP-43
    Fuyuki Kametani
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Biochem Biophys Res Commun 382:405-9. 2009
    ..Interestingly, 18 of them were located in the C-terminal glycine-rich region of TDP-43. Our results indicate that CK1-mediated phosphorylation may play a role in the pathogenesis of these diseases...
  10. ncbi TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya Ku, Tokyo 156 8585, Japan
    Biochem Biophys Res Commun 351:602-11. 2006
    ....
  11. pmc Methylene blue reduced abnormal tau accumulation in P301L tau transgenic mice
    Masato Hosokawa
    Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    PLoS ONE 7:e52389. 2012
    ..Subsequent results of Western blotting analysis revealed that this agent reduced detergent-insoluble phospho-tau. Methylene blue may have potential as a drug candidate for the treatment of tauopathy...
  12. ncbi [Frontotemporal dementia (FTD) and genetic mutations including progranulin gene]
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research
    Rinsho Shinkeigaku 48:990-3. 2008
    ..Taken together, these results suggest that elucidating the mechanism of C-terminal fragment origination may shed light on the pathogenesis of several neurodegenerative disorders involving TDP-43 proteinopathy and tauopathy...
  13. ncbi [TDP-43 proteinopathies, toward understanding of the molecular pathogenesis]
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry
    Rinsho Shinkeigaku 49:783-5. 2009
    ....
  14. ncbi TDP-43 is deposited in the Guam parkinsonism-dementia complex brains
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Brain 130:1386-94. 2007
    ..These results suggest that accumulation of TDP-43 is a common process in certain neurodegenerative disorders, including FTLD-U, ALS and G-PDC...
  15. pmc Conversion of wild-type alpha-synuclein into mutant-type fibrils and its propagation in the presence of A30P mutant
    Motokuni Yonetani
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, 156 8585 Tokyo, Japan
    J Biol Chem 284:7940-50. 2009
    ....
  16. ncbi Inhibition of alpha-synuclein fibril assembly by small molecules: analysis using epitope-specific antibodies
    Masami Masuda
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    FEBS Lett 583:787-91. 2009
    ..This strongly suggests that small molecule inhibitors bind and stabilize intermediates of amyloid fibril formation, consistent with the view that inhibitor-bound molecular species are on-pathway intermediates...
  17. doi Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models
    Makiko Yamashita
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Reearch, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    FEBS Lett 583:2419-24. 2009
    ..These findings were confirmed by immunoblot analysis. The results indicate that MB and dimebon may be useful for the treatment of ALS, FTLD-U and other TDP-43 proteinopathies...
  18. pmc Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of neurodegenerative diseases
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo 156 8585, USA
    J Biol Chem 285:34885-98. 2010
    ..Our cellular models thus provide evidence of nucleation-dependent and protein-specific polymerization of intracellular amyloid-like proteins in cultured cells...
  19. ncbi [Neurodegenerative disorders and TDP-43]
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Brain Nerve 61:161-6. 2009
    ..Elucidating the biochemical processes responsible for phosphorylation, fragmentation, and intracellular aggregation of TDP-43 may provide important insights into the pathogenesis of TDP-43 proteinopathy...
  20. doi Prion-like properties of pathological TDP-43 aggregates from diseased brains
    Takashi Nonaka
    Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya Ku, Tokyo 156 8506, Japan
    Cell Rep 4:124-34. 2013
    ..These results indicate that insoluble TDP-43 has prion-like properties that may play a role in the progression of TDP-43 proteinopathy. ..
  21. ncbi Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies
    Aasami Ishii
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    FEBS Lett 581:4711-7. 2007
    ..Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies...
  22. pmc Prion-like spreading of pathological α-synuclein in brain
    Masami Masuda-Suzukake
    Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2 1 6 Kamikitazawa, Setagaya Ku, Tokyo 156 8506, Japan
    Brain 136:1128-38. 2013
    ..This is a new mouse model of sporadic α-synucleinopathy and should be useful for elucidating progression mechanisms and evaluating disease-modifying therapy...
  23. doi Epitope mapping of antibodies against TDP-43 and detection of protease-resistant fragments of pathological TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration
    Hiroshi Tsuji
    Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Biochem Biophys Res Commun 417:116-21. 2012
    ..The antibodies and methods used in this study will be useful for the characterization of abnormal TDP-43 in human materials, as well as in vitro and animal models for TDP-43 proteinopathies...
  24. ncbi Differential diagnosis of amyotrophic lateral sclerosis from Guillain-Barré syndrome by quantitative determination of TDP-43 in cerebrospinal fluid
    Masato Hosokawa
    1Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Int J Neurosci 124:344-9. 2014
    ..4% and the specificity was 84.6%. Quantitative determination of TDP-43 concentrations in the CSF by sandwich ELISA is a potential laboratory test for differentiating ALS from peripheral motor neuropathies such as GBS. ..
  25. doi Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS
    Kotaro Ogaki
    Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan
    Parkinsonism Relat Disord 19:15-20. 2013
    ..The aim of this study was to investigate the genetic and clinical features of Japanese patients with MAPT, PGRN, or C9orf72 mutations...
  26. ncbi [Molecular dissection of TDP-43 in ALS and FTLD]
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry
    Rinsho Shinkeigaku 50:937-9. 2010
    ..These results suggest that abnormal TDP-43 produced in a cell may be transferred to different regions and propagated during disease progression...
  27. ncbi Cleavage at the carboxyl-terminus of Ku80 during apoptosis in human Jurkat T cells
    Masahiko Kato
    Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
    J Biochem 137:685-92. 2005
    ..Our study clearly shows that Ku80 is cleaved in the nucleus, and distributes in the cytoplasm during apoptosis...
  28. doi Molecular analysis and biochemical classification of TDP-43 proteinopathy
    Hiroshi Tsuji
    Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156 8506, Japan
    Brain 135:3380-91. 2012
    ..These results suggest a new clinicopathological classification of TAR DNA-binding protein 43 proteinopathies based on their molecular properties...
  29. ncbi [Analysis of alpha-synuclein and its significance]
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry
    Nihon Rinsho 62:1623-8. 2004
    ..The ubiquitination sites of soluble and filamentous alpha-synuclein were determined. These data have important implications for understanding the formation of alpha-synuclein filaments in synucleinopathy brains...
  30. ncbi Small molecule inhibitors of alpha-synuclein filament assembly
    Masami Masuda
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Biochemistry 45:6085-94. 2006
    ....
  31. ncbi Ubiquitination of alpha-synuclein
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Biochemistry 44:361-8. 2005
    ..These data may have implications for the mechanisms of the formation of alpha-synuclein deposits in alpha-synucleinopathy brains...
  32. ncbi Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya Ku, Tokyo, Japan
    Ann Neurol 55:72-9. 2004
    ..Such a biochemical divergence may be related to the neuropathological features of these diseases...
  33. ncbi [The molecular mechanisms of intracellular TDP-43 aggregates]
    Takashi Nonaka
    Department of Molecular Neur obiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Brain Nerve 61:1292-300. 2009
    ....
  34. pmc Assembly of the type III secretion apparatus of enteropathogenic Escherichia coli
    Tomoaki Ogino
    Laboratory of Bacterial Infection, Kitasato Institute for Life Sciences, Kitasato University, 5 9 1 Shirokane, Minato ku, Tokyo 108 8641, Japan
    J Bacteriol 188:2801-11. 2006
    ..These results indicate that EscC, EscD, and EscJ are required for the formation of the TTS apparatus...
  35. ncbi Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Setagaya Ku, 156 8585, Tokyo, Japan
    Neurosci Lett 342:41-4. 2003
    ..These results suggest that the degenerative process involves p62 in FTD and that the process takes place not only in neurons but also in glial cells...
  36. ncbi Cleavage of nonmuscle myosin heavy chain-A during apoptosis in human Jurkat T cells
    Masahiko Kato
    Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639
    J Biochem 137:157-66. 2005
    ....
  37. ncbi Phosphorylated alpha-synuclein is ubiquitinated in alpha-synucleinopathy lesions
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Japan
    J Biol Chem 277:49071-6. 2002
    ..These results strongly suggest that phosphorylated alpha-synuclein is targeted to mono- and diubiquitination in synucleinopathy brains, which may have implications for mechanisms of these diseases...
  38. pmc Transcriptional regulation of the hypocretin/orexin gene by NR6A1
    Susumu Tanaka
    Department of Sleep Disorders Research, Tokyo Institute of Psychiatry, Tokyo, Japan
    Biochem Biophys Res Commun 403:178-83. 2010
    ..Electroporation with Nr6a1 in the foetal hypothalamus promoted hypocretin transcription as compared to GFP-electroporation. These experiments confirmed that NR6A1 works as a regulator for hypocretin transcription...
  39. ncbi Cysteine misincorporation in bacterially expressed human alpha-synuclein
    Masami Masuda
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya ku 156 8585, Tokyo, Japan
    FEBS Lett 580:1775-9. 2006
    ..To avoid potential artefacts, we recommend use of the Y136-TAT construct for the expression of human alpha-syn...
  40. ncbi Monitoring of caspase-8/FLICE processing and activation upon Fas stimulation with novel antibodies directed against a cleavage site for caspase-8 and its substrate, FLICE-like inhibitory protein (FLIP)
    Yuichi Niikura
    Division of Cell Biology and Biochemistry, Department of Basic Medical Science, Institute of Medical Science, The University of Tokyo IMSUT, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Biochem 132:53-62. 2002
    ..Using this system, we found that Fas-susceptibility changes during U937 differentiation occur upstream of caspase-8 processing/activation...
  41. pmc Uptake and metabolism of ciclesonide and retention of desisobutyryl-ciclesonide for up to 24 hours in rabbit nasal mucosa
    Hideyuki Sato
    Teijin Institute for Biomedical Research, Teijin Pharma Limited, Asahigaoka, Hino, Tokyo, Japan
    BMC Pharmacol 7:7. 2007
    ..Retention and formation of fatty acid conjugates of des-CIC were also measured in nasal mucosa extracts postadministration of a hypotonic ciclesonide suspension (143-mug single dose)...