In search of memory complexes using a BRI2-derived peptide

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Gifu University
• Principal Investigator: Matsuda Shuji 岐阜大学, 大学院医学系研究科, 准教授 (70296721)
• Co-Investigator(Kenkyū-buntansha): 千田 隆夫 岐阜大学, 大学院医学系研究科, 教授 (10187875)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アルツハイマー病 / BRi2 / ペプチド

Outline of Final Research Achievements

Alzheimer Disease (AD) is the most prevalent dementia in modern societies. The pathogenesis of AD is poorly understood, and its therapies have much room to be improved. Amyloid beta deposits found in the brains of AD patients are processed from the precursor protein of amyloid beta, termed Alzheimer Protein Precursor (APP). We had identified BRI2, which binds and inhibits the processing of APP. This BRI2 inhibits APP processing in cultured cells, and slows the Amyloid beta deposition in AD model mice.
In this research we focused on the BRI2 peptide, which is derived from the amino acid sequence of BRI2 and inhibits the beta pathway of APP processing. We identified peroxiredoxin 1 (PRDX1), an anti-oxidative stress enzyme, as a target protein of this peptide. We also found PRDX1 is functionally required for the inhibition of APP processing by BRI2, hinting a possible link between oxidative stress and APP processing.

Free Research Field

解剖学、生化学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病(AD)の研究の焦点は、患者脳内に蓄積したベータアミロイドが毒性を呈するというアミロイド仮説に基づいているものが大部分です。しかし、アミロイドを患者脳内から除去しても病状が改善しないなど、アミロイド仮説では、理解も治療も成功しておりません。
本研究は、ADの進行を抑えるBRI2に注目し、他の研究とは別方面からADの病態を解明しようとするものです。BRI2に基づくペプチドを用いて、抗酸化作用を持つ標的蛋白質を同定し、抗酸化作用とAPPの代謝の関連を見つけています。老化のシグナルである酸化的ストレスに対抗する酵素とAPPの代謝の関連は、新しい治療の基礎になりえます。