Development of innovative aggregation inhibition strategies for amyloid proteins that cause neurodegenerative diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02602
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Sohma Youhei 和歌山県立医科大学, 薬学部, 教授 (10565518)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アミロイド / タンパク質 / 神経変性疾患 / 凝集 / 阻害 / 触媒 / 酸素化 / 立体構造

Outline of Final Research Achievements

Methodologies to suppress protein aggregation and accumulation, which will lead to treatments strategy for neurodegenerative diseases caused by the accumulation of amyloid, were studied. We have designed and synthesized artificial catalysts that photooxygenated amyloid (chemically add oxygen atoms under light irradiation conditions). As a result, we were able to reduce the amount of tau amyloid accumulated in the brain by non-invasively oxygenating amyloid in mouse brains. Furthermore, we have tackled to solve the higher-order structure of amyloid using organic chemistry-based methods, with the aim of promoting the design of inhibitors based on the three-dimensional structure information of amyloid. As a result, three-dimensional structure information of amyloid was obtained via chemically suppressing the aggregation dynamics through the introduction of artificial structures.

Free Research Field

創薬化学、ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

アミロイドタンパク質の凝集・蓄積を抑制するための革新的方法論に資する、光酸素化触媒の創製およびアミロイド立体構造の解明に成功した。特に、長波長光によってアミロイド選択的に活性化することに加え、マウス脳内でアミロイドの酸素化を促進し分解を促進するための触媒設計指針を得ることができた。さらに、得られたアミロイドの立体構造情報は、原子レベルでの阻害剤設計を可能とする点で意義深い。