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2006 Fiscal Year Final Research Report Summary

Studies on the practical diagnosis and pathomechanism of tauopathy as neurodegenerative disordrs

Research Project

Project/Area Number 16590848
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

MORI Hideo  Juntendo University, Dept.Neurol, Associate Prof, 医学部, 助教授 (30150634)

Co-Investigator(Kenkyū-buntansha) TADA Nobuhiro  JUNTENDO UNIVERSITY, Graduate School of medicine, assistant Prof, 医学部, 講師 (50338315)
SHIMURA Hideki  JUNTENDO UNIVERSITY, School of medicine, Aassistant, 医学部, 助手 (50286746)
石黒 幸一  三菱科生命研, 生命分子工学部, 主任研究員 (50374012)
KOBAYASHI Tomonori  Fukuoka University, School of medicine, assistant, 医学部, 助手 (50266053)
本井 ゆみ子  順天堂大学, 医学部, 助手 (60338407)
Project Period (FY) 2004 – 2006
Keywordstauopathy / frontotemporal dementia / parkinsonism / tau protein / phosphorylated / corticobasal degeneration / N279 / パーキンソン病
Research Abstract

1)Based on the analysis of the clinical, pathological and genetic features of the three families with tau N279K mutation, we have demonstrated that the clinical phenotype of N279K mutation was relatively uniform even in the families with unrelated founders. The pathologic changes involved the spinal cord as well as basal ganglia, and cerebral cortex and white matter.
2)We have retrospectively reviewed 8 patients with autopsy-proven corticobasal degeneration and reported the variable clinical phenotypes including marked palilalia, progressive dysarthria, progressive dysphagia, and non-fluent aphasia.
3)We transiently transfected mouse neuroblastoma cells (N18TG2) with wild-type tau or tau with the L266V mutation from a patient with familial frontotemporal dementia. Tau protein was observed in both the wild-type and L266V mutant tau transfectants, as were inclusions composed of tau phosphorylated at amino acids Thrl 81, Ser 202/Thr205, and Ser396. Inclusions immunoreactive with anti-tau antibodies AT8 and pS396 were also immunoreactive with antibodies against ubiquitin and glycogen synthase kinase 3□.
4)We have revealed that progression of motor deterioration in the model mice with P301 tau mutation was inhibited by administration of lithium.

  • Research Products

    (15 results)

All 2007 2006 2005 2004

All Journal Article (14 results) Book (1 results)

  • [Journal Article] Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein2007

    • Author(s)
      Ihara, MIhara, M. et al.
    • Journal Title

      Neuron 53・4

      Pages: 519-533

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sept4, a Component of Presynaptic Scaffold and Lewy Bodies, Is Required for the Suppression of alpha-Synuclein Neurotoxicity.2007

    • Author(s)
      Ihara M, Yamasaki N, Hagiwara A, Tanigaki A, Kitano A, Hikawa R, Tomimoto H, Noda M, Takanashi M, Mori H, Hattori N, Miyakawa T, Kinoshita M
    • Journal Title

      Neuron. 53

      Pages: 519-533

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pathologic changes of progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy2006

    • Author(s)
      Mori H.
    • Journal Title

      J Neurol 253・Suppl 3

      Pages: iii41-iii46

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Positive immunoreactivity for vesicular monoamine transporter 2 in Lewy bodies and Lewy neurites in substantia nigra.2006

    • Author(s)
      Yamamoto S, Fukae J, Mori H, Mizuno Y, Hattori N.
    • Journal Title

      Neurosci Lett. 396

      Pages: 187-191

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nuclear localization of the 20S proteasome subunit in Parkinson's disease.2006

    • Author(s)
      Nakamura A, Kitami T, Mori H, Mizuno Y, Hattori N.
    • Journal Title

      Neurosci Lett. 406

      Pages: 43-48

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prognosis of Parkinson's disease : time to stage III, IV, V, and to motor fluctuations.2006

    • Author(s)
      Sato K, Hatano T, Yamashiro K, Kagohashi M, Nishioka K, Izawa N, Mochizuki H, Hattori N, Mori H, Mizuno Y
    • Journal Title

      Mov Disord 21

      Pages: 1384-1395

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Relationship between Parkinson disease with dementia and dementia with Lewy bodies.2005

    • Author(s)
      Guo L et al.
    • Journal Title

      Parkinsonism Relat Disord 11

      Pages: 305-309

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pathological substrate of dementia in Parkinson's disease-its relation to DLB and DLBD.2005

    • Author(s)
      Mori H et al.
    • Journal Title

      Parkinsonism Relat Disord 11 Suppl 1

      Pages: S41-45

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of 8-oxoguanine DNA glycosylase (OGG1) in Parkinson's disease and related neurodegenerative disorders.2005

    • Author(s)
      Fukae J, Takanashi M, Kubo S, Nishioka K, Nakabeppu Y, Mori H, Mizuno Y, Hattori N
    • Journal Title

      Acta Neuropathol (Berl) 109

      Pages: 256-262

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Relationship between Parkinson disease with dementia and dementia with Lewy bodies.2005

    • Author(s)
      Guo L, Itaya M, Takanashi M, Mizuno Y, Mori H.
    • Journal Title

      Parkinsonism Relat Disord 11

      Pages: 305-309

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glial localization of four-repeat tau in atypical progressive supranuclear palsy.2004

    • Author(s)
      Motoi Y, et al.
    • Journal Title

      Neuropathology 24

      Pages: 60-65

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Apolipoprotein E receptor 2 is involved in neuritic plaque formation in APP sw mice.2004

    • Author(s)
      Motoi Y et al.
    • Journal Title

      Neurosci Lett 23

      Pages: 144-147

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glial localization of four-repeat tau in atypical progressive supranuclear palsy.2004

    • Author(s)
      Motoi Y, Takanashi M, Itaya M, Ikeda K, Mizuno Y, Mori H.
    • Journal Title

      Neuropathology 24

      Pages: 60-65

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Apolipoprotein E receptor 2 is involved in neuritic plaque formation in APP sw mice.2004

    • Author(s)
      Motoi Y, Itaya M, Mori H, Mizuno Y, Iwasaki T, Hattori H, Haga S, Ikeda K.
    • Journal Title

      Neurosci Lett 23

      Pages: 144-147

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Neurological CPC2006

    • Author(s)
      水野美邦, 森 秀生
    • Total Pages
      370
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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