The role of autophagy in the maintenance of homeostasis in brain

• Project/Area Number: 16K08613
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University (2017-2018); The University of Tokyo (2016)
• Principal Investigator: Kuma Akiko 大阪大学, 医学系研究科, 特任准教授(常勤) (30392377)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: オートファジー / 選択的基質 / 神経変性疾患 / 神経疾患

Outline of Final Research Achievements

Autophagy is a degradation system within a cell. In this process, small portion of cytoplasmic components are engulfed by autophagosomes, transported to lysosomes and degraded. It has been reported that autophagy-deficient mice show phenotypes similar to neurodegenerative diseases. In order to clarify the cause, we performed MS analysis of the autophagy-deficient mouse brain and found that substrates, regulators and receptors for autophagy are highly accumulated. We focused on some of them, and we are in process of analyzing their role in autophagy and the relationship with the pathological condition in detail.

Academic Significance and Societal Importance of the Research Achievements

オートファジーは、アルツハイマーやパーキンソン病などの神経変性疾患との関連が強く示唆されており、脳におけるオートファジーの生理機能およびその破綻による神経症状の発症機序を理解することは、基礎生物学的にも医学的にも重要である。

Research Products

• [Journal Article] Transgenic rescue of Atg5-null mice from neonatal lethality with neuron-specific expression of ATG5: Systemic analysis of adult Atg5-deficient mice. (2017)
  • Author(s): Yoshii SR, Kuma A, Mizushima N.
  • Journal Title: Autophagy Volume: 13 Issue: 4 Pages: 763-764
  • DOI: 10.1080/15548627.2017.1280221
  • Peer Reviewed
• [Journal Article] Autophagy-monitoring and autophagy-deficient mice. (2017)
  • Author(s): Kuma A, Komatsu M, Mizushima N.
  • Journal Title: Autophagy Volume: 13 Issue: 10 Pages: 1619-1628
  • DOI: 10.1080/15548627.2017.1343770
  • Peer Reviewed / Open Access
• [Journal Article] Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons. (2016)
  • Author(s): Yoshii SR, Kuma A, Akashi T, Hara T, Yamamoto A, Kurikawa Y, Itakura E, Tsukamoto S, Shitara H, Eishi Y, Mizushima N.
  • Journal Title: Developmental cell Volume: 39 Issue: 1 Pages: 116-130
  • DOI: 10.1016/j.devcel.2016.09.001
  • Peer Reviewed
• [Presentation] Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons (2017)
  • Author(s): Akiko Kuma, Saori Yoshii, Takumi Akashi, Taichi Hara, Atsushi Yamamoto, Yoshitaka Kurikawa, Eisuke Itakura, Satoshi Tsukamoto, Hiroshi Shitara, Yoshinobu Eishi, Noboru Mizushima
  • Organizer: Joint Japan-Korea-China Young Investigator Conference
  • Place of Presentation: Korea
  • Year and Date: 2017-02-19
  • Int'l Joint Research
• [Presentation] Transgenic rescue of <I>Atg5</I>-null mice from neonatal lethality with neuron-specific expression of ATG5 (2017)
  • Author(s): 久万 亜紀子
  • Organizer: 第69回日本細胞生物学会
  • Invited
• [Book] 遺伝子制御の新たな主役 栄養シグナル (2016)
  • Author(s): 久万 亜紀子
  • Total Pages: 7
  • Publisher: 羊土社