Masato Hasegawa

Summary

Affiliation: Tokyo Institute of Psychiatry
Country: Japan

Publications

  1. 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
  2. ncbi [Frontotemporal dementia: tau mutations, deposition, and molecular mechanisms of neuronal cell death]
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research
    Rinsho Shinkeigaku 44:879-81. 2004
  3. ncbi Four-repeat tau-positive Pick body-like inclusions are distinct from classic Pick bodies
    Yumiko Motoi
    Acta Neuropathol 110:431-3. 2005
  4. 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
  5. ncbi Biochemistry and molecular biology of tauopathies
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Neuropathology 26:484-90. 2006
  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 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
  8. 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
  9. 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
  10. 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

Detail Information

Publications71

  1. 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...
  2. ncbi [Frontotemporal dementia: tau mutations, deposition, and molecular mechanisms of neuronal cell death]
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research
    Rinsho Shinkeigaku 44:879-81. 2004
    ..In tauopathies, neuronal cell death may occur with multiple defects or abnormalities arisen directly or indirectly from hyperphosphorylation of tau and formation of oligomer or filamentous tau...
  3. ncbi Four-repeat tau-positive Pick body-like inclusions are distinct from classic Pick bodies
    Yumiko Motoi
    Acta Neuropathol 110:431-3. 2005
  4. 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...
  5. ncbi Biochemistry and molecular biology of tauopathies
    Masato Hasegawa
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Neuropathology 26:484-90. 2006
    ....
  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 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...
  8. 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
    ....
  9. 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
    ....
  10. 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...
  11. 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..
  12. 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...
  13. doi Phosphorylated TDP-43 in Alzheimer's disease and dementia with Lewy bodies
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Acta Neuropathol 117:125-36. 2009
    ..There may be genetic factors, such as mutations or genetic variants of PGRN underlying the co-occurrence of abnormal deposition of TDP-43, tau and alpha-synuclein...
  14. 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...
  15. doi Accumulation of phosphorylated TDP-43 in brains of patients with argyrophilic grain disease
    Hiroshige Fujishiro
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Acta Neuropathol 117:151-8. 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. 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
    ....
  19. 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...
  20. ncbi Tau-positive fine granules in the cerebral white matter: a novel finding among the tauopathies exclusive to parkinsonism-dementia complex of Guam
    Mineo Yamazaki
    Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu shi, Tokyo, Japan
    J Neuropathol Exp Neurol 64:839-46. 2005
    ..The TFGs were hyperphosphorylated tau-positive structures that may be formed by a different mechanism from that used to produce cortical NFTs...
  21. 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...
  22. 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...
  23. 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
    ....
  24. doi Phosphorylated and cleaved TDP-43 in ALS, FTLD and other neurodegenerative disorders and in cellular models of TDP-43 proteinopathy
    Tetsuaki Arai
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
    Neuropathology 30:170-81. 2010
    ..Understanding the mechanism of phosphorylation and truncation of TDP-43 and aggregate formation may be crucial for clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapeutics...
  25. 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. ..
  26. 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...
  27. 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...
  28. ncbi [Component of ubiquitin-positive inclusions in ALS]
    Masato Hasegawa
    Department of Molecular Neur obiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Brain Nerve 59:1171-7. 2007
    ..This article reviews the ubiquitin-positive inclusions in ALS and the recent discovery of TDP-43 in tau-negative inclusions in FTLD-U and ALS. We also discuss the biological implications of these findings for the pathogenesis of ALS...
  29. 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...
  30. 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...
  31. 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
    ....
  32. ncbi Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins
    Sayuri Taniguchi
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    J Biol Chem 280:7614-23. 2005
    ..Identification of small molecule inhibitors of heparin-induced assembly of tau will form a starting point for the development of mechanism-based therapies for the tauopathies...
  33. 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...
  34. 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...
  35. 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. ..
  36. ncbi Pathological features of FTLD-FUS in a Japanese population: analyses of nine cases
    Zen Kobayashi
    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Neurology, JA Toride Medical Center, Toride, Ibaraki, Japan
    J Neurol Sci 335:89-95. 2013
    ..Redistribution of FUS from the nucleus to the cytoplasm could be associated with the formation of abnormal FUS aggregates in FTLD-FUS. ..
  37. 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...
  38. ncbi Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies
    Yuri Umeda
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    Neurosci Lett 359:151-4. 2004
    ..These results suggest that decrease of 3R tau mRNA associated with loss of neuronal element may largely contribute to the increased ratio of 4R/3R tau mRNA in sporadic tauopathies...
  39. doi Occurrence of basophilic inclusions and FUS-immunoreactive neuronal and glial inclusions in a case of familial amyotrophic lateral sclerosis
    Zen Kobayashi
    Department of Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo, Japan
    J Neurol Sci 293:6-11. 2010
    ..These findings support the idea that both BIs and FUS-ir structures are pathological hallmarks of a subset of ALS cases...
  40. ncbi Unique tauopathy in Fukuyama-type congenital muscular dystrophy
    Yuko Saito
    Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    J Neuropathol Exp Neurol 64:1118-26. 2005
    ..This anomalous phosphorylation of tau may be related to the development of the cortical dysgenesis in FCMD and may shed light on the biologic function of tau in the development of the central nervous system...
  41. doi Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies
    Kimiko Obi
    Department of Neurology, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo, 113 8421, Japan
    Exp Neurol 210:409-20. 2008
    ..The procession from Abeta to neurite pathology in the cerebral cortex of AD and DLB may be unifiable...
  42. 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...
  43. 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
    ....
  44. 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...
  45. 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...
  46. 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
    ....
  47. ncbi Fibrillogenic nuclei composed of P301L mutant tau induce elongation of P301L tau but not wild-type tau
    Hirofumi Aoyagi
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    J Biol Chem 282:20309-18. 2007
    ..Thus, the interaction between fibrillogenic nuclei and monomeric protein appears to play an important role in the mechanism of tau filament assembly...
  48. ncbi Accumulation of phosphorylated alpha-synuclein in aging human brain
    Yuko Saito
    Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
    J Neuropathol Exp Neurol 62:644-54. 2003
    ....
  49. 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...
  50. 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...
  51. ncbi Regulation of membrane association and kinase activity of Cdk5-p35 by phosphorylation of p35
    Ko Sato
    Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan
    J Neurosci Res 85:3071-8. 2007
    ....
  52. ncbi A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology
    Tomonori Kobayashi
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    Ann Neurol 53:133-7. 2003
    ..Recombinant tau with a L266V mutation showed a reduced ability to promote microtubule assembly, which may be the primary effect of the mutation...
  53. ncbi alpha-Synuclein is phosphorylated in synucleinopathy lesions
    Hideo Fujiwara
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Nat Cell Biol 4:160-4. 2002
    ..Furthermore, phosphorylation of alpha-synuclein at Ser 129 promoted fibril formation in vitro. These results highlight the importance of phosphorylation of filamentous proteins in the pathogenesis of neurodegenerative disorders...
  54. ncbi Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila
    Makio Takahashi
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Neurosci Lett 336:155-8. 2003
    ..These results suggest that accumulation and phosphorylation of alpha-synuclein is recapitulated in neurons of alpha-synuclein transgenic Drosophila, that underscores the relevance of this model to human synucleinopatheis...
  55. ncbi Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with p35, p25, or p39
    Fumika Sakaue
    Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachiohji, Tokyo 192 039, Japan
    J Biol Chem 280:31522-9. 2005
    ....
  56. ncbi Dyrk1A phosphorylates alpha-synuclein and enhances intracellular inclusion formation
    Eun Joo Kim
    Department of Biology, College of Science, Yonsei University, Seoul 120 749, Korea
    J Biol Chem 281:33250-7. 2006
    ..These findings suggest alpha-synuclein inclusion formation regulated by Dyrk1A, potentially affecting neuronal cell viability...
  57. ncbi Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation
    Shintaro Hayashi
    Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
    Ann Neurol 51:525-30. 2002
    ..Thus, we consider that the Arg5His mutation is an authentic tau gene abnormality responsible for the patient's tau pathology and late-onset dementia...
  58. ncbi Biochemical characterization of the core structure of alpha-synuclein filaments
    Hirotomo Miake
    Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Biol Chem 277:19213-9. 2002
    ....
  59. ncbi Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes
    Kenji Sakai
    Department of Pathology, Brain Research Institute, University of Niigata, 1 757 Asahimachi, Niigata 951 8585, Japan
    Acta Neuropathol 112:341-8. 2006
    ..Finally, in both cases, the pathological diagnosis of CBD was considered to be appropriate. However, the tau pathology affecting the subcortical white matter astrocytes was very unusual for the disease...
  60. ncbi Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration
    Koichi Wakabayashi
    Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan
    Neuropathology 26:66-71. 2006
    ..This phenomenon implies that phagocytosis of Abeta coincides with production of phosphorylated tau in the same reactive astrocytes...
  61. pmc Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes
    Philipp J Kahle
    Laboratory for Alzheimer s and Parkinson s Disease Research, Department of Biochemistry, Ludwig Maximilians University, D 80336 Munich, Germany
    EMBO Rep 3:583-8. 2002
    ..Thus, ectopic expression alpha SYN in OLs might initiate salient features of MSA pathology...
  62. ncbi Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy
    Kazuo Yamakawa
    Department of Neurology, Juntendo Urayasu Hospital, Chiba, Japan
    Neuropathology 26:586-91. 2006
    ..This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease...
  63. pmc Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice
    Masaki Ikeda
    Department of Neurology, Gunma University Graduate School of Medicine, 3 39 22 Showa machi, Maebashi, Gunma 371 8511, Japan
    Am J Pathol 166:521-31. 2005
    ..These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD)...
  64. pmc Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2
    Guadalupe Sabio
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem J 380:19-30. 2004
    ....
  65. ncbi Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy
    Makoto Nishie
    Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu cho, 036 8562, Hirosaki, Japan
    Acta Neuropathol 107:292-8. 2004
    ..Thus, the widespread accumulation of phosphorylated alpha-synuclein in both glial and neuronal cells is a pathological feature in patients suffering from MSA...
  66. ncbi Phosphorylated alpha-synuclein in normal mouse brain
    Yu Hirai
    Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194 8511, Japan
    FEBS Lett 572:227-32. 2004
    ..Relative prominence and age sensitivity of this phenomenon in the striatum may be relevant to the pathogenesis of Parkinson's disease...
  67. ncbi Ultra-high field NMR studies of antibody binding and site-specific phosphorylation of alpha-synuclein
    Hiroaki Sasakawa
    Department of Structural Biology and Biomolecular Engineering, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3 1 Tanabe dori, Mizuho ku, Nagoya 467 8603, Japan
    Biochem Biophys Res Commun 363:795-9. 2007
    ....
  68. pmc Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies
    Manuela Neumann
    Department of Neuropathology, Ludwig Maximilians University, Munich, Germany
    J Clin Invest 110:1429-39. 2002
    ..The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions...
  69. ncbi A clinical and neuropathological study of an unusual case of sporadic tauopathy. A variant of corticobasal degeneration?
    Shinji Ohara
    Department of Neurology, National Chushin Matsumoto Hospital, 811 Kotobuki, Matsumoto 399 0021, Japan
    Neurosci Lett 330:84-8. 2002
    ..Our findings, taken together with those in previous similar case reports, indicate that the case represents an atypical form of corticobasal degeneration or a new variant of sporadic tauopathy...
  70. ncbi Alpha-synuclein accumulates in Purkinje cells in Lewy body disease but not in multiple system atrophy
    Fumiaki Mori
    Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan
    J Neuropathol Exp Neurol 62:812-9. 2003
    ..No such inclusions were observed in MSA, tauopathies, or controls. These findings indicate that Purkinje cells are also the victims of a-synuclein pathology in PD and DLB, but not in MSA...
  71. ncbi A novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17
    Anna Kowalska
    Institute of Human Genetics, Polish Academy of Sciences, ul Strzeszynska 32, 60 479 Poznan, Poland
    J Appl Genet 43:535-43. 2002
    ..Our study confirmed that the T --> C 3'E10 +11 mutation, as the other 5' splice site mutations of tau exon 10, modifies alternative splicing of exon 10...