The analysis of clearance mechanism of oxygenated Abeta

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06653
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hori Yukiko 東京大学, 大学院薬学系研究科(薬学部), 講師 (80610683)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 神経変性疾患 / 神経科学

Outline of Final Research Achievements

Alzheimer disease is caused by the accumulation of amyloid, called as amyloid β peptide (Aβ) and tau, in the brain. We previously developed an artificial photo-oxygenation system using a low molecular weight catalytic compound, photocatalyst. And we also have revealed the possibility that this amyloid selective photo-oxygenation inhibited the aggregation and facilitated the clearance of already formed amyloid. However, the mechanism of facilitated clearance by photo-oxygenation was unclear.
In this study, we found that the structural and biochemical properties of amyloid were changed by photo-oxygenation. We also revealed that microglia were responsible cells in brain for facilitated degradation of photo-oxygenated Aβ, and that lysosomal degrading enzymes within these cells were involved in degradation. These results suggest that photo-oxygenation have possibility as a novel therapeutic strategy against Alzheimer disease.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

高齢者認知症の多くを占めるADは、大きな社会問題となっている。脳内でのアミロイドの蓄積がAD発症の原因であることから、アミロイド形成を抑制し、既に蓄積したアミロイドを効率よく除去することがAD根本治療戦略として考えられているが、未だ根本治療法確立には至っていない。本研究成果は、凝集Aβやタウに対する光酸素化法の新規AD根本治療戦略としての可能性を示した点で意義がある。また光酸素化触媒はアミロイドに共通の立体構造に対して反応し活性化することから、パーキンソン病や筋萎縮性側索硬化症などの、AD以外のアミロイド形成・蓄積を原因とする多くの神経変性疾患に対しても有用である可能性が期待される。