Spatial and temporal control of intracellular aggregates by photo-oxygenation catalyst

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19480
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pharmaceutical Sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Tomita Taisuke 東京大学, 大学院薬学系研究科(薬学部), 教授 (30292957)
• Research Collaborator: Hori Yukiko
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 神経変性疾患 / タンパク質凝集 / 光触媒

Outline of Final Research Achievements

Several lines of evidence suggest that the intracellular aggregates comprised of fibrillized proteins are involved in the pathogenesis of neurodegenerative diseases. In addition, recently intercellular propagation mechanism of aggregated protein that transform the normal cells to the pathological cells has been highlighted. In this research, applicants examined the effect of photo-oxygenation catalyst, which detoxifies the aggregated proteins by oxygenation reaction under light, on the tau protein aggregation and propagation. Tau is deposited in the brains of Alzheimer disease. We found that the photo-oxygenation inhibited the tau aggregation and the propagation activity of tau fibril. These results indicated that the dynamics of intracellular aggregates can be regulated by these small compounds.

Free Research Field

病態生化学

Academic Significance and Societal Importance of the Research Achievements

様々な神経変性疾患発症の原因となる細胞内凝集体の動態機構の解明は、多くの疾患治療を考える上で重要な研究課題である。しかし現在までに時空間的にその動態を解析した例はなく、光酸素化触媒による細胞内凝集体の時空間的制御は、神経変性疾患発症メカニズム研究においてインパクトのある実験系を提示できたと言える。さらに光酸素化触媒の応用は時空間的に制御された画期的治療法の開発に繋がる可能性があり、我が国の科学技術イノベーションに大きく資するものと考えられる。