NSAIDs inhibit forming oligomers and fibrils by binding to the structure of <beta>-amyloid and <alpha>-synuclein protein aggregates

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06498
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Chemical biology
• Research Institution: Hirosaki University
• Principal Investigator: Hirohata Mie 弘前大学, 医学研究科, 助教 (50806552)
• Research Collaborator: Shoji Mikio ; Sato Kaoru
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: ケミカルバイオロジー / 蛋白凝集 / アミロイドβ / αシヌクレイン / オリゴマー / 分子間相互作用 / アルツハイマー病 / パーキンソン病

Outline of Final Research Achievements

The oligomeric forms of amyloid β-protein (Aβ) or α-synuclein (αS) play a critical role in the development of Alzheimer’s disease (AD) or Parkinson’s disease (PD). Epidemiological studies have revealed that therapeutic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and PD. We show that NSAIDs have anti-oligomerization and anti-fibrillization effects on Aβ(1-40), Aβ(1-42) and αS in vitro at physiological pH and temperature, by using nucleation-dependent polymerization monitored by thioflavin fluorescence, atomic force microscopy, electron microscopy, and photo-induced cross-linking of unmodified proteins (PICUP) followed by SDS-PAGE. Three-dimensional fluorescence spectroscopic analyses demonstrated that some NSAIDs interacted with Aβs or αS oligomers. We speculated that NSAIDs inhibit forming oligomers and fibrils by binding to the structure of their aggregates. NSAIDs could be key molecules for the preventive agents for AD and PD.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果から，NSAIDsはアルツハイマー病およびパーキンソン病の予防薬および病態修飾薬の有力な候補分子となる可能性があることが示唆された．この分野の検討は，これまで国際的にも報告がなく，NSAIDsとの分子間相互作用に基づいたアルツハイマー病およびパーキンソン病の病態修飾薬を開発する上でも極めて重要な貢献ができると考えられる．