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Molecular biological study on the cause and pathogenesis of amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Kii peninsula of Japan

Research Project

Project/Area Number 19390239
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry (2008)
Mie University (2007)

Principal Investigator

KUZUHARA Shigeki  National Center of Neurology and Psychiatry, 病院長 (70111383)

Co-Investigator(Kenkyū-buntansha) KOKUBO Yasumasa  三重大学医学部, 神経内科学, 講師 (60263000)
SASAKI Ryogen  三重大学医学部, 神経内科学, 助教 (60303723)
KUWANO Ryouzou  新潟大学脳研究所, 附属生命科学リソース研究センター, 教授 (20111734)
伊藤 伸朗  三重大学, 医学部附属病院, 助教 (10362344)
Co-Investigator(Renkei-kenkyūsha) TOMIYAMA Hiroyuki  順天堂大学, 医学部・神経内科, 助教 (20515069)
HATTORI Nobutaka  順天堂大学, 医学部・神経内科, 教授 (80218510)
TSUJI Syouji  東京大学, 医学部・神経内科, 教授 (70150612)
HARA Kenjyu  新潟大学, 脳研究所・神経内科 (10377195)
MURAYAMA Shigeo  東京都老人総合研究所, 高齢者ブレインバンク, 部長 (50183653)
SAITO Yuuko  国立精神・神経センター病院, 医長 (60344066)
HASEGAWA Nmasato  東京都精神医学総合研究所, 分子神経生物学研究チーム, 部長 (10251232)
IWATSUBO Takeshi  東京大学, 医学部・神経病理学部門 (50223409)
MORIMOTO Satoru  三重大学, 医学部, 学生
AKATSUKA Naomi  三重大学, 神経内科, 技術補佐
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2008: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2007: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Keywords紀伊半島 / 筋萎縮性側索硬化症 / パーキンソン認知症複合 / 遺伝子 / アルツハイマー神経原線維変化 / TDP-43 / 酸化ストレス / タウ蛋白 / タウオパチー / 認知症 / パーキンソン症候群 / グアム島
Research Abstract

紀伊半島の一部集落に多発する神経風土病の筋萎縮性側索硬化症・パーキンソン認知症複合(ALS/PDC)類似疾患で知られているほぼ全ての原因遺伝子を調べ、異常変異は認められなかった。病態と発症に関して、脳のアルツハイマー神経原線維変化の分布様式はALSとPDCでほぼ同じであった。脳と脊髄にはTDP-43の蓄積が認められ、生化学的にはタウ/TDP-43異常蓄積症と考えられた。尿中の酸化ストレスマーカーが有意に上昇しており、神経変性に参加ストレスの関与が推定された。タウとTDP-43の蓄積を起こして神経変性が進行する仕組みと、遺伝子の関与の解明が今後の課題である。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (42 results)

All 2009 2008 2007 Other

All Journal Article (25 results) (of which Peer Reviewed: 13 results) Presentation (14 results) Book (3 results)

  • [Journal Article] Increased oxidative stress in patients with amyotrophic lateral sclerosis/parkinsonism-dementia comlex in the Kii Peninsula, Japan.2009

    • Author(s)
      Morimoto S, Kuzuhara S, Kokubo Y
    • Journal Title

      Mov Disord 24

      Pages: 123-126

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased oxidative stress in patients with amyotrophic lateral sclerosis/parkinsonism-dementia comlex in the Kii Peninsula, Japan2009

    • Author(s)
      Morimoto S, Kuzuhara S, Kokubo Y
    • Journal Title

      Mov Disord 24

      Pages: 123-126

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation analyses in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula, Japan.2008

    • Author(s)
      Tomiyama H, Kokubo Y, Sasaki R, Li Y, Imamichi Y, Funayama M, Mizuno Y, Hattori N, Kuzuhara S
    • Journal Title

      Mov Disord 23

      Pages: 2344-2348

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 厚生労働省特定疾患治療研究事業臨床調査個人票の集計結果からみたパーキンソン病患者の現況.2008

    • Author(s)
      谷口彰, 成田有吾, 内藤寛, 葛原茂樹
    • Journal Title

      臨床神経学 48

      Pages: 106-113

    • NAID

      10021187102

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 紀伊・西ニューギニアの ALS.2008

    • Author(s)
      葛原茂樹
    • Journal Title

      Clin Neurosci 26

      Pages: 292-297

    • Related Report
      2008 Final Research Report
  • [Journal Article] ALS患者の脳と脊髄への TDP-43蛋白の異常蓄積とTDP-43遺伝子変異の発見.2008

    • Author(s)
      葛原茂樹
    • Journal Title

      難病と在宅ケア 14

      Pages: 31-33

    • NAID

      40016323706

    • Related Report
      2008 Final Research Report
  • [Journal Article] LS研究の最近の進歩 : ALSとTDP-43.2008

    • Author(s)
      葛原茂樹
    • Journal Title

      臨床神経 48

      Pages: 625-633

    • Related Report
      2008 Final Research Report
  • [Journal Article] DP-43と神経変性疾患 紀伊半島ALS/PDCとTDP-43.2008

    • Author(s)
      葛原茂樹
    • Journal Title

      神経内科 68

      Pages: 565-570

    • Related Report
      2008 Final Research Report
  • [Journal Article] Mutation analyses in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula, Japan2008

    • Author(s)
      Tomiyama H, Kokubo Y, Sasaki R, Li Y, Imamichi Y, Funayama M, Mizuno Y, Hattori N, Kuzuhara S
    • Journal Title

      Mov Disord 23

      Pages: 2344-2348

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 厚生労働省特定疾患治療研究事業臨床調査個人票の集計結果からみたパーキンソン病患者の現況2008

    • Author(s)
      谷口彰, 成田有吾, 内藤寛, 葛原茂樹
    • Journal Title

      臨床神経 48

      Pages: 106-113

    • NAID

      10021187102

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 紀伊・西ニューギニアのALS2008

    • Author(s)
      葛原茂樹
    • Journal Title

      Clin Neurosci 26

      Pages: 292-297

    • Related Report
      2008 Annual Research Report
  • [Journal Article] ALS患者の脳と脊髄へのTDP-43蛋白の異常蓄積とTDP-43遺伝子変異の発見2008

    • Author(s)
      葛原茂樹
    • Journal Title

      難病と在宅ケア 14

      Pages: 31-33

    • NAID

      40016323706

    • Related Report
      2008 Annual Research Report
  • [Journal Article] ALS研究の進歩:ALSとTDP-432008

    • Author(s)
      葛原茂樹
    • Journal Title

      臨床神経 48

      Pages: 625-633

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TDP-43と神経変性疾患 紀伊半島ALS/PDCとTDP-432008

    • Author(s)
      葛原茂樹
    • Journal Title

      神経内科 68

      Pages: 565-570

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Similar topographical distribution of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism-dementia complex in people living in the Kii peninsula of Japan suggests a single tauopathy.2007

    • Author(s)
      Mimuro M, Kokubo Y, Kuzuhara S
    • Journal Title

      Acta Neuropathol 113

      Pages: 653-658

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 第48回日本神経学会総会シンポジウム. 西大西洋地域の筋萎縮側索硬化症/パーキンソン痴呆複合(ALS/PDC)と関連神経変性疾患 紀伊 ALS/PDC (牟婁病)の歴史、概念、疫学.2007

    • Author(s)
      葛原茂樹
    • Journal Title

      臨床神経 47

      Pages: 962-965

    • Related Report
      2008 Final Research Report
  • [Journal Article] 第48回日本神経学会総会 会長講演. 紀伊半島の牟婁(むろ)病(筋萎縮性側索硬化症・パーキンソン・認知症複合)2007

    • Author(s)
      葛原茂樹
    • Journal Title

      臨床神経 47

      Pages: 695-702

    • Related Report
      2008 Final Research Report
  • [Journal Article] 第48回日本神経学会総会 シンポジウム 西大西洋地域の筋萎縮性側索硬化症/パーキンソン・認知症複合(ALS/PDC)と関連神経変性疾患. 紀伊半島の筋萎縮性側索硬化症/パーキンソン・認知症複合の臨床、神経病理学的研究.2007

    • Author(s)
      小久保康昌
    • Journal Title

      臨床神経 47

      Pages: 966-969

    • Related Report
      2008 Final Research Report
  • [Journal Article] 第48回日本神経学会総会 シンポジウム 西大西洋地域の筋萎縮性側索硬化症/パーキンソン・認知症複合(ALS/PDC)と関連神経変性疾患.紀伊ALS/PDCの分子遺伝学的.2007

    • Author(s)
      原 賢寿、桑野良三、宮下哲典、小久保康昌、佐々木良元、中原安雄、後藤 順、西澤正豊、葛原茂樹、辻 省次
    • Journal Title

      臨床神経 47

      Pages: 974-976

    • Related Report
      2008 Final Research Report
  • [Journal Article] 特集 ALS-研究と診療の進歩 紀伊ALS再訪ーALS-parkinsonism-dementia complex としての新しい概念、疫学、原因についての考察.2007

    • Author(s)
      葛原茂樹
    • Journal Title

      BRAIN and NERVE 59

      Pages: 1065-1074

    • Related Report
      2008 Final Research Report
  • [Journal Article] Similar topographical distribution of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism dementia complex in people living in the Kii peninsula of Japan suggests a single tauopathy2007

    • Author(s)
      Mimuro M, Kokubo Y, Kuzuhara S
    • Journal Title

      Acta Neuropathol 113

      Pages: 653-658

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pressure ulcers in ALS patients on admission at a university hospital in Japan2007

    • Author(s)
      Hayashi T, Narita Y, Okugawa N, Hamaguchi E, Shibahara M, Kuzuhara S
    • Journal Title

      Amyotrophic Lateral Sclerosis 8

      Pages: 310-313

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model2007

    • Author(s)
      Shibata N, S, Kokubo Y, Kuzuhara S, et. al.
    • Journal Title

      Neuropathology 27

      Pages: 49-61

    • NAID

      10021235172

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRPM7 is not associated with amyotrophic lateral sclerosis-parkinsonism dementia complex in the Kii peninsula of Japan.

    • Author(s)
      Hara K, Kokubo Y, Ishiura H, Fukuda Y, Miyashita A, Kuwano R, Sasaki R, Goto J, Nishizawa M, Kuzuhara S, Tsuji S:
    • Journal Title

      Am J Med Genet Part B (in press)

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] TRPM7 is not associated with amyotrophic lateral sclerosis-parkinsonism dementia complex in the Kii peninsula of Japan

    • Author(s)
      Hara K, Kokubo Y, Ishiura H, Fukuda Y, Miyashita A, Kuwano R, Sasaki R, Goto J, Nishizawa M, Kuzuhara S, Tsuji S
    • Journal Title

      Am J Med Genet Part B (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Immunohistochemical study on phosphorylated TDP-43 protein in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula of Japan.2008

    • Author(s)
      Kokubo Y, Endo M, ArainT, Akiyama H, Hasegawa M, Kuzuhara S
    • Organizer
      6th International Conference on Frontotemporal Dementias Rotterdam
    • Place of Presentation
      The Netherlands
    • Year and Date
      2008-09-05
    • Related Report
      2008 Final Research Report
  • [Presentation] Immunohistochemical study on phosphorylated TDP-43 protein in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula of Japan2008

    • Author(s)
      Kokubo Y, Endo M, Arai T, Akiyama H, Hasegawa M, Kuzuhara S
    • Organizer
      6th International Conference on Frontotemporal Dementias
    • Place of Presentation
      Rotterdam, The Netherlands
    • Year and Date
      2008-09-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] 紀伊半島に多発するALS」風土病としてALS研究から、日本と世界のALS の原因解明へ2008

    • Author(s)
      葛原茂樹
    • Organizer
      日本ALS協会群馬県支部総会
    • Year and Date
      2008-05-31
    • Related Report
      2008 Final Research Report
  • [Presentation] 「紀伊半島に多発するALS」風土病としてALS研究から、日本と世界のALSの原因解明へ2008

    • Author(s)
      葛原茂樹
    • Organizer
      日本ALS協会群馬県支部総会
    • Place of Presentation
      群馬県社会福祉総合センター
    • Year and Date
      2008-05-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] 紀伊半島の牟婁病(筋萎縮性側索硬化症/パーキンソン認知症複合 : ALS/PDC)2007

    • Author(s)
      3.葛原茂樹
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-16
    • Related Report
      2008 Final Research Report
  • [Presentation] Immunohistochemical study on tau isoform in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula of Japan.2007

    • Author(s)
      Kokubo Y,Saito Y, Murayama S, Kuzuhara S
    • Organizer
      18^<th> International Symposium on ALS/MND
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2008 Final Research Report
  • [Presentation] 第48回日本神経学会総会シンポジウム. 西大西洋地域の筋萎縮側索硬化症/パーキンソン痴呆複合(ALS/PDC)と関連神経変性疾患紀伊ALS/PDC(牟婁病)の歴史2007

    • Author(s)
      葛原茂樹
    • Organizer
      第48回日本神経学会総会,
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] 紀伊半島ALS/parkinsonism-dementia complexにおけるTDP-43蓄積2007

    • Author(s)
      葛原茂樹
    • Organizer
      第48回日本神経病理学会総会
    • Place of Presentation
      船堀東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Immunohistochemical study on TDP-43 protein in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula of Japan.2007

    • Author(s)
      Kokubo Y, Saito Y, Murayama S, Kuzuhara S
    • Organizer
      第26回日本認知症学会
    • Place of Presentation
      大阪市 大阪国際会議場
    • Related Report
      2008 Final Research Report
  • [Presentation] 紀伊半島ALS/parkinsonism-dementia complexにおけるTDP-43蓄積2007

    • Author(s)
      葛原 茂樹
    • Organizer
      第48回日本神経病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] Duration of career as a coordinator and thought of attendance at a bad-news telling session for ALS patients in Japan.2007

    • Author(s)
      Yugo Narita, Michiko Nakai, Shigeki Kuzuhara
    • Organizer
      18th International Symposium on ALS/MND
    • Place of Presentation
      Toronto
    • Related Report
      2007 Annual Research Report
  • [Presentation] I mmunohistochemical study on tau isoform in amyotronhic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula of Japan2007

    • Author(s)
      Y, Kokubo, Y, Saito, S, Murayama, S, Kuzuhara
    • Organizer
      18th International Symposium on ALS/MND
    • Place of Presentation
      Toronto
    • Related Report
      2007 Annual Research Report
  • [Presentation] 葛原茂樹: 紀伊ALS/PDCの歴史,概念,疫学2007

    • Author(s)
      葛原 茂樹
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2007 Annual Research Report
  • [Presentation] Clinical aspects,imaging and neuropathology of Kii ALS/PDC2007

    • Author(s)
      小久保 康昌
    • Organizer
      第48回日本神経学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2007 Annual Research Report
  • [Book] 精神・神経疾患画像アトラス(葛原茂樹 監修)2007

    • Author(s)
      葛原 茂樹
    • Total Pages
      167
    • Publisher
      メディカルレビュー社
    • Related Report
      2007 Annual Research Report
  • [Book] Huntington病, 今日の診断基準(大田 健, 奈良 信雄 編集)2007

    • Author(s)
      葛原 茂樹
    • Total Pages
      1
    • Publisher
      南江堂,東京
    • Related Report
      2007 Annual Research Report
  • [Book] 中毒性疾患, 最新自律神経学(宇尾野 公義, 入來正躬 監修)2007

    • Author(s)
      葛原 茂樹
    • Total Pages
      10
    • Publisher
      新興医学出版社,東京
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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