Identification of protein kinase(s) involved in abnormal phosphorylation of alpha-synuclein

• Project/Area Number: 15300119
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: HASEGAWA Masato Tokyo Metropolitan Organization for Medical Research, Tokyo Institute of Psychiatry, Head of department, 東京都精神医学総合研究所, 副参事研究員 (10251232)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥14,000,000 (Direct Cost: ¥14,000,000); Fiscal Year 2005: ¥4,100,000 (Direct Cost: ¥4,100,000); Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000); Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
• Keywords: alpha-synuclein / phosphorylation / ubiquitination / filaments / casein kinase 2 / Parkinson's disease / Lewy body / レヴィー小体 / レヴィー小体型痴呆 / 多系統萎縮症

Research Abstract

Filamentous inclusions made of alpha-synuclein in nerve cells or glial cells are the defining neuropathological feature of a group of neurodegenerative diseases which include Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. In these so-called "alpha-synucleinopathies", a-synuclein is deposited in a hyperphosphorylated form at Ser129 in the carboxyl-terminal region. In this study, we have attempted to identify a protein kinase that phosphorylates Ser129 of alpha-synuclein in brain, using a monoclonal antibody P-Ser129 which specifically recognizes phosphorylated Ser129 of alpha-synuclein. Recombinant human alpha-synuclein was incubated with brain extracts from 6-week rat in the presence of ATP, and the protein kinase activity was detected by immunoblotting of phosphorylated alpha-synuclein with the P-Ser129 antibody. The protein kinase activity was partially purified by ammonium sulfate fractionation and anion exchange column chromatography, and cha racterized by immunoblotting and some inhibitors. The protein kinase activity was precipitated with 33% ammonium sulfate and eluted with 0.4-0.5M NaCl on a Q-Sepharose column chromatography. Immunoblot analysis of these fractions with anti-casein kinase 2 (CK2) antibody revealed that CK2 catalytic subunit was enriched through these steps. The protein kinase activities in the partially purified fraction and crude brain extracts were dramatically inhibited by heparin, a well-known specific inhibitor of CK2. These findings strongly suggest that CK2 may be the major protein kinase in brain that phosphorylates Serl29 of alpha-synuclein. In DLB brains, aberrant CK2 immunoreactivities were also observed in the Sarkosyl-insoluble fraction where the hyperphosphorylated alpha-synuclein was enriched, whereas no such immunoreactivity was detected in the fraction from control brains. These results suggest that CK2 may be involved in the abnormal phosphorylation of alpha-synuclein in alpha-synucleinopathies.

Research Products

• [Journal Article] Small Molecule Inhibitors of alpha-Synuclein Filament Assembly. (2006)
  • Author(s): Masuda, M., Szuki, N., Goedrt, M., Hasegawa, M.
  • Journal Title: Biochemistry (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Biochemistry and molecular biology of tauopathies. (2006)
  • Author(s): Hasegawa, M.
  • Journal Title: Neuropathology (in press)
  • NAID: 10019264205
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration. (2006)
  • Author(s): Wakabayashi K, Mori F, Hasegawa M et sl.
  • Journal Title: Neuropathology 26 Pages: 66-71
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cysteine misincorporation in bacterially expressed human alpha-synuclein. (2006)
  • Author(s): Masuda, M., Dohmae, N., Goedert,, Hasegawa, M.
  • Journal Title: FEBS Lett. 580 Pages: 1775-79
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cysteine misincorporation in bacterially expressed human alpha-synuclein. (2006)
  • Author(s): Masuda M, Dohmae N, Nonaka T, Oikawa T, Hisanaga S, Goedert M, Haseaewa M
  • Journal Title: FEBS Left 580 Pages: 1775-1779
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cysteine misincorporation in bacterially expressed human alpha-synuclein. (2006)
  • Author(s): Masuda, M., Dohmae, N., Goedert, M., Hasegawa, M.
  • Journal Title: FEBS Lett. 580 Pages: 1775-1779
• [Journal Article] Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration. (2006)
  • Author(s): Wakabayashi K, Mori F, Hasegawa M, et al.
  • Journal Title: Neuropathology 26 Pages: 66-71
• [Journal Article] Small Molecule Inhibitors of alpha-Synuclein Filament Assembly. (2006)
  • Author(s): Masuda, M., Suzuki, N., Goedert, M., Hasegawa, M.
  • Journal Title: Biochemistry (in press)
• [Journal Article] Tau-positive fine granules in the cerebral white matter : a novel finding exclusive to parkinsonism-dementia complex of Guam among the tauopathies (2005)
  • Author(s): Yamazaki, M., Hasegawa, M., Mori, O.et al.
  • Journal Title: J. Neuropathol. Exp. Neurol 64 Pages: 839-46
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Unique tauopathy in Fukuyama-type congenital muscular dystrophy (2005)
  • Author(s): Saito, Y., N, Hasegawa, M, Murayama, S.
  • Journal Title: J. Neuropathol. Exp. Neurol 64 Pages: 839-46
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. (2005)
  • Author(s): Ikeda, M., Shoji, M., Kawatai, T, Hasegawa.M.et al.
  • Journal Title: Am. J. Pathol 166 Pages: 521-31
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols and porphyrins (2005)
  • Author(s): Taniguchi, S., Suzuki, N...., Goedert, M., Hasegawa, M.
  • Journal Title: J. Biol. Chem 280 Pages: 7614-23
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phosphorylation of FTDP-17 mutant TAU by cyclin-dependent kinase 5 complexed with p35, p25, or p39. (2005)
  • Author(s): Sakaue, F., Saito, T., Hasegawa, M., Hisanaga, S
  • Journal Title: J. Biol. Chem 280 Pages: 31522-29
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Four-repeat tau-positive Pick body-like inclusions are distinct from classic Pick bodies. (2005)
  • Author(s): Motoi, Y., Hasegawa, M., Mizumo, Y., Mori, H
  • Journal Title: Acta Neuropathol.(Berl) 110 Pages: 431-33
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ubiquitination of alpha-synuclein. (2005)
  • Author(s): Nonaka T, Iwatsubo T, Hasegawa M:
  • Journal Title: Biochemistry 44 Pages: 361-368
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibition of heparin-induced tau filament formation by phenothiazines, polvphenols and porphyrins. (2005)
  • Author(s): Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert M, Hasegawa M
  • Journal Title: J Biol Chem 280 Pages: 7614-7623
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tau-positive fine granules in the cerebral white matter : a novel finding exclusive to parkinsonism-dementia complex of Guam among the tauopathies. (2005)
  • Author(s): Yamazaki M, Hasegawa M, Mori O, Murayama S, Tsuchiya K, Ikeda K, Chen K-M, Katayama Y, Oyanagi K
  • Journal Title: J Neuropathol Exp Neurol 64 Pages: 839-846
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phosphorylation of FTDP-17 mutant TAU by cyclin-dependent kinase 5 complexed with p35, p25, or p39. (2005)
  • Author(s): Sakaue, F., Saito, T., Sato, Y., Asada, A., Ishiguro, K., Hasegawa, M., Hisanaga, S.
  • Journal Title: J Biol Chem 280 Pages: 31522-31529
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Four-repeat tau-positive Pick body-like inclusions are distinct from classic Pick bodies. (2005)
  • Author(s): Motoi Y, Iwamoto H, Itaya M, Kobayashi T, Hasegawa M, Yasuda M, Mizuno Y, Mori H.
  • Journal Title: Acta Neuropathol (Berl) 110 Pages: 431-433
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Unique tauopathy in Fukuyama-type congenital muscular dystrophy. (2005)
  • Author(s): Saito Y, Motoyoshi Y, Kashima T, Izumiyama-Shimoharma M, Toda T, Nakano I, Hasegawa M, Murayama S.
  • Journal Title: J Neuropathol Exp Neurol 64 Pages: 1118-1126
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. (2005)
  • Author(s): Ikeda, M., Shoji, M., Kawarai, T., Kawarabayashi, T., Matsubara, E., Murakami, T., Sasaki, A., Tomidokoro, Y., Ikarashi, Y., Kuribara, H., Ishiguro, K., Hasegawa, M., Yen, S.H., Chishti, M.A., Harigaya, Y., Abe, K., Okamoto, K., St George-Hyslop.P., Westaway, D.
  • Journal Title: Am J Pathol 166 Pages: 521-531
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ubiquitination of alpha-synuclein. (2005)
  • Author(s): Nonaka, T., Iwatsubo, T., Hasegawa, M.
  • Journal Title: Biochemistry 44 Pages: 361-368
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. (2005)
  • Author(s): Ikeda, M., Shoji, M., Kawarai, T, Hasegawa, M., et al.
  • Journal Title: Am.J.Pathol 166 Pages: 521-531
• [Journal Article] Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols and porphyrins (2005)
  • Author(s): Taniguchi, S., Suzuki, N., Goedert, M., Hasegawa, M.
  • Journal Title: J.Biol.Chem 280 Pages: 7614-7623
• [Journal Article] Phosphorylation of FTDP-17 mutant TAU by cyclin-dependent kinase 5 complexed with p35,p25,or p39. (2005)
  • Author(s): Sakaue, F., Saito, T., Hasegawa, M., Hisanaga, S
  • Journal Title: J.Biol.Chem 280 Pages: 31522-31529
• [Journal Article] Four-repeat tau-positive Pick body-like inclusions are distinct from classic Pick bodies. (2005)
  • Author(s): Motoi, Y., Hasegawa, M., Yasuda, M., Mizuno, Y., Mori, H
  • Journal Title: Acta Neuropathol.(Berl) 110 Pages: 431-433
• [Journal Article] Tau-positive fine granules in the cerebral white matter : a novel finding exclusive to parkinsonism-dementia complex of Guam among the tauopathies (2005)
  • Author(s): Yamazaki, M., Hasegawa, M., Mori, O., et al.
  • Journal Title: J.Neuropathol.Exp.Neurol 64 Pages: 839-846
• [Journal Article] Unique tauopathy in Fukuyama-type congenital muscular dystrophy. (2005)
  • Author(s): Saito, Y., N, Hasegawa, M., Murayama, S.
  • Journal Title: J.Neuropathol.Exp.Neurol 64 Pages: 839-846
• [Journal Article] Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice. (2005)
  • Author(s): Ikeda M, Hasegawa M, Westaway D, et al.
  • Journal Title: Am J Pathol 166 Pages: 521-531
• [Journal Article] Ubiquitination of alpha-synuclein. (2005)
  • Author(s): Nonaka T, Iwatsubo T, Hasegawa M
  • Journal Title: Biochemistry 44 Pages: 361-368
• [Journal Article] Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols and porphyrins. (2005)
  • Author(s): Taniguchi S, Suzuki N, Masuda M, Hisanaga SI, Iwatsubo T, Goedert M, Hasegawa M
  • Journal Title: J Biol Chem 280 Pages: 7614-7623
• [Journal Article] Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia patients with multiple system atrophy. (2004)
  • Author(s): Nishie M, Mori F, Hasegawa M, Takehashi H, Wakabayashi K et al.
  • Journal Title: Acta Neuropathol 107 Pages: 292-298
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phosphorylated alpha-synuclein in normal mouse brain. (2004)
  • Author(s): Hirai Y, Fujita SC, Iwatsubo T, Hasegawa M
  • Journal Title: FEBS Lett 572 Pages: 227-232
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Frontopemporal dementia with Pick-type histology associated with Q336R mutation in tau gene. (2004)
  • Author(s): Pickering-Brown SM, Hasegawa M, Mann DMA et al.
  • Journal Title: Brain 127 Pages: 1415-1426
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stress-and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD95 by activation of SAPK3/p38g and ERKI1/ERK2. (2004)
  • Author(s): Sabio G, Hasegawa M, Goedert M, Garner C, Cuenda A et al.
  • Journal Title: Biochem J 380 Pages: 19-30
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies. (2004)
  • Author(s): Umeda Y, Taniguchi S, Arima K, Piao Y-S, Mann D, Hasegawa M et al.
  • Journal Title: Neurosci. Lett 359 Pages: 151-154
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of amino-terminal cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration. (2004)
  • Author(s): Arai T, Ikeda K, Akiyama H, Nonaka T, Hasegawa M et al.
  • Journal Title: Ann Neurol 55 Pages: 72-79
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein. (2004)
  • Author(s): Tniguchi S, McDonagh AM, Hasegawa M et al.
  • Journal Title: Neuropathol Appl Neurobiol 30 Pages: 1-18
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phosphorylated alpha-synuclein in normal mouse brain. (2004)
  • Author(s): Hirai Y, Fujita SC, Iwatsubo T, Hasegawa M
  • Journal Title: FEBS Left 572 Pages: 227-232
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. (2004)
  • Author(s): Nishie M, Mori F, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K
  • Journal Title: Acta Neuropathol 107 Pages: 292-298
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2. (2004)
  • Author(s): Sabio G, Reuver S, Feijoo C, Hasegawa M, Thomas GM, Centeno F, Kuhlendahl S Leal-Ortiz S, Goedert M, Garner C, Cuenda A
  • Journal Title: Biochem J 380 Pages: 19-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mann DMA : Frontopemporal dementia with Pick-type histology associated with Q336R mutation in tam gene. (2004)
  • Author(s): Pickering-Brown SM, Baker M, Nonaka T, Ikeda K, Sharma S, Mackenzie J, Simpson SA, Moore JW, Snowden JS, de Silva R, Revesz T, Hasegawa M, Hutton M
  • Journal Title: Brain 127 Pages: 1415-1426
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of amino-terminal cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration. (2004)
  • Author(s): Arai T, Ikeda K, Akiyama H, Nonaka T, Hasegawa M, Ishiguro K, Iritani S, Tsuchiya K, Iseki E, Yagishita S, Oda T, Mochizuki A
  • Journal Title: Ann Neurol 55 Pages: 72-79
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies. (2004)
  • Author(s): Umeda Y, Taniguchi S, Arima K, Piao Y-S, Takahashi H, Iwatsubo T, Mann D, Hasegawa M
  • Journal Title: Neurosci.Lett 359 Pages: 151-154
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein. (2004)
  • Author(s): Taniguchi S, McDonagh AM, Pickering-Brown SA, Umeda Y, Iwatsubo T, Hasegawa M, Mann DMA
  • Journal Title: Neuropathol Appl Neurobiol 30 Pages: 1-18
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy. (2004)
  • Author(s): Nishie M, Mori F, Hasegawa M, Takahashi H, Wakabayashi K, et al.
  • Journal Title: Acta Neuropathol 107 Pages: 292-298
• [Journal Article] Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies. (2004)
  • Author(s): Umeda Y, Taniguchi S, Arima K, Piao Y-S, Mann D, Hasegawa M, et al.
  • Journal Title: Neurosci.Lett 359 Pages: 151-154
• [Journal Article] Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD95 by activation of SAPK3/p38g and ERK1/ERK2. (2004)
  • Author(s): Sabio G, Hasegawa M, Goedert M, Garner C, Cuenda A, et al.
  • Journal Title: Biochem J 380 Pages: 19-30
• [Journal Article] Frontopemporal dementia with Pick-type histology associated with Q336R mutation in tau gene. (2004)
  • Author(s): Pickering-Brown SM, Hasegawa M, Hutton M, Mann DMA, et al.
  • Journal Title: Brain 127 Pages: 1415-1426
• [Journal Article] alpha-synuclein accumulates in purkinje cells in Lewy body disease but not in multiple system atrophy. (2003)
  • Author(s): Mori F, Piao Y-S, Hayashi S, Fujiwara H, Hasegawa M et al.
  • Journal Title: J Neuropathol Exp Neurol 62 Pages: 812-819
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62. (2003)
  • Author(s): Arai T, Nonaka T, Hasegawa M et al.
  • Journal Title: Neurosci Lett 342
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Accumulation of phosphorylated alpha-synuclein in aging human brain. (2003)
  • Author(s): Saito Y, Kawashima A, Ruberu NN, Hasegawa M et al.
  • Journal Title: J Neuropathol Exp Neurol 62 Pages: 644-645
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 1. Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila (2003)
  • Author(s): Takahashi M, Kanuka H, Fujiwara H, Hasegawa M et al.
  • Journal Title: Neurosci Lett 336 Pages: 155-158
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique pathology (2003)
  • Author(s): Kobayashi T, Ota S, Tanaka K, Ito Y, Hasegawa M et al.
  • Journal Title: Ann Neurol 53 Pages: 133-137
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] alpha-synuclein accumulates in purkinje cells in Lewy body disease but not in multiple system atrophy. (2003)
  • Author(s): Mori F, Piao Y-S, Hayashi S, Fujiwara H, Hasegawa M, Yoshimoto M, Iwatsubo T, Takahashi H, Wakabayashi K
  • Journal Title: J Neuropathol Exp Neurol 62 Pages: 812-819
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62. (2003)
  • Author(s): Arai T, Nonaka T, Hasegawa M, Akiyama H, Yoshida M, Hashizume Y, Tsuchiya K, Oda T, Ikeda K
  • Journal Title: Neurosci Lett 342 Pages: 41-44
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Accumulation of phosphorylated alpha-synuclein in aging human brain. (2003)
  • Author(s): Saito Y, Kawashima A, Ruberu NN, Fujiwara H, Koyama S, Sawabe M, Arai T, Nagura H, Yamanouchi H, Hasegawa M, Iwatsubo T, Murayama S
  • Journal Title: J Neuropathol Exp Neurol 62 Pages: 644-654
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is recapitulated in alpha-synuclein transgenic Drosophila (2003)
  • Author(s): Takahashi M, Kanuka H, Fujiwara H, Hasegawa M, Miura M, Iwatsubo T
  • Journal Title: Neurosci Lett 336 Pages: 155-158
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau apthology. (2003)
  • Author(s): Kobayashi T, Ota S, Tanaka K, Ito Y, Hasegawa M, Umeda Y, Motoi Y, Takanashi M, Yasuhara M, Anno M, Mizuno Y, Mori H
  • Journal Title: Ann Neurol 53 Pages: 133-137
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Saito Y, et al.: "Accumulation of phosphorylated alpha-synuclein in aging human brain."J Neuropathol Exp Neurol. 62. 644-654 (2003)
• [Publications] Arai T, et al.: "Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62."Neurosci Lett. 342. 41-44 (2003)
• [Publications] Mori F, et al.: "alpha-synuclein accumulates in purkinje cells in Lewy body disease but not in multiple system atrophy."J Neuropathol Exp Neurol. 62. 812-819 (2003)
• [Publications] Taniguchi S, et al.: "The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein."Neuropathol Appl Neurobiol. 30. 1-18 (2004)
• [Publications] Arai T, et al.: "Identification of amino-terminal cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration."Ann Neurol. 55. 72-79 (2004)
• [Publications] Nishie M, et al.: "Accumulation of phosphorylated alpha-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy."Acta Neuropathol. (in press).
• [Publications] Pickering-Brown SM, et al.: "Frontopemporal dementia with Pick-type histology associated with Q336R mutation in tau gene."Brain. (in press).
• [Publications] Sabio G, et al.: "Stress- & mitogen-induced phosphorylation of the synapse-associated protein SAP9O/PSD95 by activation of SAPK3/p38γ & ERK1/ERK2"Biochem J. (in press).
• [Publications] Umeda Y, et al.: "Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies."Neurosci Lett. (in press).