Role of MITOL in Alzheimer's disease

• Project/Area Number: 16K15224
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: YANAGI Shigeru 東京薬科大学, 生命科学部, 教授 (60252003)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ユビキチンリガーゼ / アルツハイマー病 / MAM / ミトコンドリア

Outline of Final Research Achievements

Although mitochondrial ubiquitin ligase MITOL is suggested as a risk factor for Alzheimer's disease (AD), implication of MITOL in the pathology of AD is unknown. Here we generated and analyzed neuron-specific MITOL-knockout AD model mice. We found that MITOL knockout increases high toxic soluble amyloid-beta, resulting in exacerbation of symptoms of AD. This result suggests that MITOL regulates aggregation or conformation of amyloid-beta, thereby attenuating cytotoxicity of amyloid-beta.

Research Products

• [Journal Article] アルツハイマー病におけるMAMの本当の役割 (2017)
  • Author(s): 武田 啓佑, 柳 茂
  • Journal Title: BIO Clinica Volume: 32 Pages: 782-787
• [Journal Article] Rescue of CAMDI deletion-induced delayed radial migration and psychiatric behaviors by HDAC6 inhibitor. (2016)
  • Author(s): Fukuda, T., Nagashima, S., Abe, T., Kiyonari, H., Inatome, R. and Yanagi, S.
  • Journal Title: EMBO. Rep Volume: 17 Pages: 1785-1798
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulation of B cell differentiation by the ubiquitin-binding protein TAX1BP1. (2016)
  • Author(s): Matsushita, N., Suzuki, M., Ikebe, E., Nagashima, S., Inatome, R., Asano, K., Tanaka, M., Matsushita, M., Kondo, E., Iha, H., and Yanagi, S.
  • Journal Title: Sci. Rep Volume: 6 Issue: 1 Pages: 31266-31266
  • DOI: 10.1038/srep31266
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ミトコンドリアユビキチンリガーゼMITOLによるＡβ凝集制御と病態解析 (2017)
  • Author(s): 伊藤直樹, 宇田葵, 武田啓佑, 稲留涼子, 柳茂
  • Organizer: 第17回日本ミトコンドリア学会年会
• [Presentation] ミトコンドリア膜型ユビキチンリガーゼMITOLによる老人斑の形成制御と病態解析 (2017)
  • Author(s): 宇田葵, 伊藤直樹, 武田啓佑, 稲留涼子, 柳茂
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）