A・generation regulated by the degradation of Rer1 through ERAD

• Project/Area Number: 23700425
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Iwate Medical University
• Principal Investigator: TANABE Chiaki 岩手医科大学, 薬学部, 助教 (00552902)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 老化性痴呆疾患 / アルツハイマー病 / γセクレターゼ / ERAD / synoviolin / Rer1 / アミロイドβ

Research Abstract

Alzheimer ’s disease (AD) is characterized by the deposition of A・, which is generated by ・-secretase . We previously reported that synoviolin and/orHerp, which are involved in ER -associated degradation (ERAD), enhance A・generation,but the mechanism is unknown. In this study, we clarified that Syn regulates the assembly of the ・-secretase complex via the degradation of Rer1, which results in the generation of A・.

Research Products

• [Journal Article] アルツハイマー病にかかわるプロテアーゼ活性調節機構の解明を目指して (2013)
  • Author(s): 田邉千晶、前田智司、駒野宏人
  • Journal Title: 臨床検査 Volume: vol.57 Pages: 110-110
• [Journal Article] The ubiquitin ligase synoviolin up-regulates amyloid β production by targeting a negative regulator of γ-secretase, Rer1, for degradation. (2012)
  • Author(s): Tanabe C, Maeda T, Zou K, Liu J, Liu S, Nakajima T, Komano H.
  • Journal Title: J Biol Chem. Volume: 287 Issue: 53 Pages: 44203-44211
  • DOI: 10.1074/jbc.m112.365296
  • Peer Reviewed
• [Journal Article] Localization of mature neprilysin in lipid rafts. (2012)
  • Author(s): Sato K, Tanabe C, Yonemura Y, Watahiki H, Zhao Y, Yagishita S, Ebina M, Suo S, Futai E, Murata M, Ishiura S.
  • Journal Title: J. Neurosci. Res. Volume: 90 Issue: 4 Pages: 870-877
  • DOI: 10.1002/jnr.22796
  • Peer Reviewed
• [Journal Article] ER-stress-inducible Herp, facilitates the degradation of immature nicastrin. Biochim (2011)
  • Author(s): Marutani, T., Maeda, T., Tanabe, C ., Zou, K., Araki, W., Kokame, K., Michikawa, M. and Komano, H
  • Journal Title: Biophys. Acta Volume: 1810 Pages: 790-798
  • Peer Reviewed
• [Presentation] Synoviolin is involved in the ubiquitination of Rer1 and regulates the generation of amyloid bet (2012)
  • Author(s): Chiaki Tanabe, Tomoji Maeda, Kun Zou, Junjun Liu, Syuyu Liu, Toshihiro Nakajima, Hiroto Komano
  • Organizer: XIIIth International Symposium on Proteinase inhibitors and Biological
  • Place of Presentation: Control. Slovenia
• [Presentation] SynoviolinによるRer1分解を介したAβ産生制御 (2012)
  • Author(s): 田邉千晶、前田智司、鄒鶤、劉俊俊、劉〓余、中島利博、駒野宏人
  • Organizer: 第17回日本病態プロテアーゼ学会
  • Place of Presentation: オークラアクトシティホテル浜松、静岡
• [Presentation] SynoviolinによるRer1分解を介したAβ産生制御 (2012)
  • Author(s): ○田邉千晶、前田智司、鄒鶤、劉俊俊、Shuyu Liu、中島利博、駒野宏人
  • Organizer: 第17回日本病態プロテアーゼ学会
  • Place of Presentation: オークラアクトシティホテル浜松
• [Presentation] Synoviolin is involved in the ubiquitination of Rer1 and regulates the generation of amyloid beta (2012)
  • Author(s): ○Chiaki Tanabe, Tomoji Maeda, Kun Zou, Junjun Liu, Syuyu Liu, Toshihiro Nakajima, Hiroto Komano
  • Organizer: XIIIth International Symposium on Proteinase inhibitors and Biological Control
  • Place of Presentation: Slovenia
• [Presentation] Synoviolin is involved in the degradation of Rer1, thereby modulating A β generation (2011)
  • Author(s): 田邉千晶、前田智司、鄒鶤、Liu Junjun 、Liu Shuyu、駒野宏人
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 国立京都国際会館、京都
• [Presentation] αとγセクレターゼの解析 (2011)
  • Author(s): 田邉千晶
  • Organizer: 日本認知症学会主催-認知症研究を知る若手研究者の集まり
  • Place of Presentation: あいち健康プラザ、愛知県大府市
• [Presentation] Synoviolin is involved in the degradation of Rer1, thereby modulating Aβ generation. (2011)
  • Author(s): 田邉千晶
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都