Pivotal roles of p62 and selective autophagy in tau deposition and consequent neurodegeneration revealed with tauopathy mouse models

• Project/Area Number: 23700431
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: ONO Maiko 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 研究員 (70595876)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: タウ / p62 / 選択的オートファジー / 神経細胞死 / アルツハイマー病 / 神経原線維変化

Research Abstract

In Alzheimer’s disease, cytotoxicity exerted by abnormal tau is considered to be one of the main causes of neuronal death. Results from the present study indicate that selective autophagy and p62, a ubiquitinated cargo receptor mediating selective autophagy, are closely involved in neuronal death provoked by abnormal tau. p62 exerted neuroprotection against tau pathologies by eliminating nonfibrillar hyperphosphorylated tau species and sequestering hyperphosphorylated tau into cell bodies. Moreover, our findings suggested that insufficient capacity of p62 for processing of abnormal tau induces neuron death under tau accumulation.

Research Products

• [Presentation] Pivotal roles of p62 and selective autophagy in tau deposition and consequent neurodegeneration revealed with tauopathy mouse models (2013)
  • Author(s): Maiko Ono, Bin Ji, Masaki Tokunaga, Masaaki Komatsu, Tetsuro Ishii, Tetsuya Suhara and Makoto Higuchi
  • Organizer: BRAIN 2013
  • Place of Presentation: Shanghai China
• [Presentation] Pivotal roles of p62 and selective autophagy in tau deposition and consequent neurodegeneration revealed with tauopathy mouse models (2013)
  • Author(s): Maiko Ono
  • Organizer: BRAIN 2013
  • Place of Presentation: Shanghai
• [Presentation] Selective autophagy in neurons and its involvement in the tau pathogenesis (2012)
  • Author(s): Maiko Ono, Bin Ji, Masaki Tokunaga, Takeharu Minamihisamatsu, Masahiro Maruyama, Jun Maeda, Masaaki Komatsu, Tetsuro Ishii, Eiji Warabi, Toru Yanagawa, Tetsuya Suhara and Makoto Higuchi
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancouver Canada
• [Presentation] Selective autophagy in neurons and its involvement in the tau pathogenesis (2012)
  • Author(s): Maiko Ono
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancouver
• [Presentation] Selective autophagy in neurons and its involvement in the tau pathogenesis (2011)
  • Author(s): Maiko Ono, Bin Ji, Masahiro Maruyama, Jun Maeda, Takeharu Minamihisamatsu, Tetsuya Suhara, Makoto Higuchi
  • Organizer: 日本神経科学学会 第34回大会
  • Place of Presentation: 横浜
• [Presentation] 神経細胞におけるタウ病理発現への選択的オートファジーの関与 (2011)
  • Author(s): 小野麻衣子
  • Organizer: 日本神経科学学会
  • Place of Presentation: パシフィコ横浜
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks] 分子神経イメージング研究プログラム
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks]
  • URL: http://www.nirs.go.jp/seika/brain/index.html