• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

神経変性疾患、特にリソゾーム蓄積症の病態形成にオートファジーが果たす役割について

Research Project

Project/Area Number 19044023
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionJuntendo University (2008)
Osaka University (2007)

Principal Investigator

小池 正人  Juntendo University, 医学部, 准教授 (80347210)

Co-Investigator(Kenkyū-buntansha) 柴田 昌宏  新潟大学, 医歯学系, 准教授 (10343253)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2008: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2007: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsリソソーム / オートファジー / カテプシン / ダブルノックアウトマウス / LC3 / p62 / ユビキチン / オートフアジー / ノックアウトマウス / GROD / A170 / SOSTM1
Research Abstract

本年度新たにカテプシンDとp62とのダブルノックアウトマウスを作成することに成功したが、神経病理学的所見はカテプシンD単独欠損マウスと異なる点は見いだすことが出来なかった。一方最近様々なリソソーム蓄積症においてオートファジーが抑制されているという報告が相次いでいる。カテプシンD欠損マウスにて、ユビキチン・p62強陽性の構造物が存在する理由として、当初オートファジーの阻害された結果蓄積している構造物と考えられたが、申請者らがカテプシンDとAtg7およびp62とのダブルノックアウトマウスを用いて遺伝学的に解析したところ、カテプシンD欠損マウスのこのようなユビキチン陽性の構造物は、オートファジー依存的にむしろ増大し、p62の有無に影響されないことから、これらの構造物はKomatsuらがAtg7欠損マウスで報告した凝集体とは全く別の構造物であることを強く示唆する結果を得た (Koike et.al.., 投稿準備中) 。また、カテプシンD/Atg7ダブルノックアウトマウス神経細胞体においては異常なリソゾーム様構造物の蓄積がカテプシンD単独欠損マウスと同様認められた。これはカテプシンD/Atg7ダブルノックアウトマウスの異常なリソゾーム内にはエンドサイトーシスないしマクロオートファジー以外のオートファジー経路によりリソソームに取り込まれた基質が分解されずに蓄積している可能性がある。以上の着眼点を基に、カテプシンD/Atg7ダブルノックアウトマウスとカテプシンD単独ノックアウトマウスを比較検討し、カテプシンD欠損マウスの病態形成におけるオートファジーの関与についてその実体を検討中である。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (30 results)

All 2009 2008 2007

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (14 results) Book (1 results)

  • [Journal Article] Autophagy-Physiology and Pathophysiology2008

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

      Histochem Cell Biol 129

      Pages: 407-420

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagic neuron death in neonatal brain ischemia/hvnoxia2008

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

      Autophagy 4

      Pages: 404-408

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of Csk in neural crest lineages causes corneal anomaly by der egulating collagen fibril organization and cell motility2008

    • Author(s)
      Takatsuka A, et.al.
    • Journal Title

      Dev Biol 315

      Pages: 474-488

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological and biochemical signs of age-related neurodegene rative changes in Klotho mutant mice2008

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

      Neuroscience 152

      Pages: 924-941

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inefficient phagosome maturation in infant macrophages2008

    • Author(s)
      Saito F, et.al.
    • Journal Title

      Biochem Biophys Res Commun 375

      Pages: 113-118

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human herpesvirus-6 induces MVB formation and virus egress occ urs via an exosomal release pathway2008

    • Author(s)
      Mori Y, Koike M, et.al.(equal contributors)
    • Journal Title

      Traffic 9

      Pages: 1728-1742

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus2008

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

      Nat Cell Biol 10

      Pages: 1135-1145

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Autophagy Prevents Hippocampal Pyramidal Neuron Deatn after Hypoxic-Ischemic Injury.2008

    • Author(s)
      Koike, et. al.
    • Journal Title

      Am.J.Pathol 172

      Pages: 454-469

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Developing Post-Mitotic Mammalian Neurons In Vivo Lacking Apaf-1 Undergo Programmed Cell Death by a Caspase-Independent, Non-Apoptotic Pathway Involving Autophagy.2008

    • Author(s)
      Oppenheim, et. al.
    • Journal Title

      J. Neurosci. 28

      Pages: 1490-1497

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Participation of autophagy in renal ischemia/reperfusion injury.2008

    • Author(s)
      Suzuki, et. al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 368

      Pages: 300-306

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lysosomal Degradation of Nuclear DNA by Dnase II-like Acid Dnase in Cortical Fiber Cells of Mouse Eye Lens.2007

    • Author(s)
      Nakahara, et. al.
    • Journal Title

      FEBS J 274

      Pages: 3055-3064

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RGS18 acts as a negative regulator of osteoclastogenesis by modulating acid-sening OGR1/NFAT signaling pathway.2007

    • Author(s)
      Iwai, et. al.
    • Journal Title

      J Bone Miner Res. 22

      Pages: 1612-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of Tim-4 as a phosphatidylserine receptor.2007

    • Author(s)
      Miyanishi, et. al.
    • Journal Title

      Nature 450

      Pages: 435-439

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.2007

    • Author(s)
      Komatsu, et. al.
    • Journal Title

      Cell 131

      Pages: 1149-1163

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a Recombinant Oka Varicella Vaccine Expressing Mumps Virus Hemagglutinin-Neuraminidase Protein as a Polyvalent Live Vaccine.2007

    • Author(s)
      Somboonthum, et. al.
    • Journal Title

      Vaccine 25

      Pages: 8741-8755

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] エンドソームアダプターp18とリン酸化シグナリング2008

    • Author(s)
      名田茂之, ら
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化等会大会合同大会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] Acidification of the the Golgi apparatus is regualated by GPHR, a novel anion channel, and critical for glycosylation2008

    • Author(s)
      Maeda, et.al.
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] The role of macroautophagy in the pathogenesis of lysosomal st orage disease due to cathepsin D deficiency2008

    • Author(s)
      Koike, et.al.
    • Organizer
      Neuroscience 2008, 38th Annual Meeting Society for Neuroscience
    • Place of Presentation
      Washington Convention Center
    • Year and Date
      2008-11-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Lysosomal cathepsin D in neurons is in part delivered f rom elial cells2008

    • Author(s)
      Shibata, et.al.
    • Organizer
      Neuroscience 2008, 38th Annual Meeting Society for Neuroscience
    • Place of Presentation
      Washington Convention Center
    • Year and Date
      2008-11-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 低酸素-脳虚血負荷後の海馬錐体細胞の細胞死におけるオートファジーの関与について2008

    • Author(s)
      小池正人, ら
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2008-07-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] マウス脳におけるカテプシンDの再取り込み2008

    • Author(s)
      柴田昌宏, ら
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2008-07-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] エタノール細胞障害における赤ワインと白ワインエキスの修復能の効果2008

    • Author(s)
      塩崎元子, ら
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2008-07-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Human herpesvirus-6 induces MVB formation and virus egress via an exosomal release pathway2008

    • Author(s)
      Mori and Koike, et.al.
    • Organizer
      第60会日本細胞生物学会大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-07-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Selective autophagy regulates formation of cytoplasmic inclusions.2007

    • Author(s)
      Komatsu, et. al.
    • Organizer
      第30回日本分子生物学会年会 第80回日本生化学会大会合同大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] Involvement of autophagy in neurons of the hippocampus after adult mouse hypoxic-ischemic injury.2007

    • Author(s)
      Koike, et. al.
    • Organizer
      76th Annual Meeting Society for Neuroscience
    • Place of Presentation
      サンデイエゴ
    • Year and Date
      2007-11-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] カテプシンD欠損に伴うリソソーム蓄積症の病態形について2007

    • Author(s)
      小池正人
    • Organizer
      第50回日本神経化学会大会、第17回日本神経回路学会大会合同大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-09-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] 中枢神経特異的カテプシンD欠損による神経性セロイドリポフスチン蓄積症類似症状の誘導2007

    • Author(s)
      柴田昌宏
    • Organizer
      第50回日本神経化学会大会、第17回日本神経回路学会大会合同大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-09-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] Posssible roles of LC3, ubiquitin, and P62 in the accumulation of lysosomes in neurons deficient in Cathepsin D.2007

    • Author(s)
      Koike, et. al.
    • Organizer
      7th IBRO World Congress of Neuroscience
    • Place of Presentation
      メルボルン
    • Year and Date
      2007-07-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] A mouse with low exprrssiion of Cathepsin D is a model animal of neuronal Ceroid Lipofuscinosis.2007

    • Author(s)
      Shibata, et. al.
    • Organizer
      7th IBRO World Congress of Neuroscience
    • Place of Presentation
      メルボルン
    • Year and Date
      2007-07-14
    • Related Report
      2007 Annual Research Report
  • [Book] Chapter 3 Autophagic neuron death.Method in Enzymology In : Autophagy in Disease and Clinical Applications, Part C Ed. Daniel J. Klionsky2009

    • Author(s)
      Uchiyama Y, et.al.
    • Publisher
      Elsevier Inc
    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi