In search of tau accumulation inhibitors in vivo

Research Project

Project/Area Number	16K07050
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Nerve anatomy/Neuropathology
Research Institution	Gakushuin University
Principal Investigator	Yoshiike Yuji 学習院大学, 理学部, 研究員 (90415331)
Project Period (FY)	2016-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	タウオパチー / アミロイド / 神経原線維変化 / タンパク質変性 / ショウジョウバエ / アルツハイマー病 / 脳神経疾患
Outline of Final Research Achievements	Accumulation of tau protein, which constitutes the main component of neurofibrillary tangles seen as the pathological hallmark of Alzheimer's disease, well correlates with the degree of cognitive decline. In this research, I have built in vivo screening platform by using drosophila for the aim of search of such compounds that suppress tau aggregation. Evidence showing accumulation of tau aggregates by age in this fly model expressing human tau was obtained both biochemically and morphologically. Based on the exploration by using this model, a compound with its property to inhibit tau aggregation was identified. And the patent for this discovery along with its versatility was granted.
Academic Significance and Societal Importance of the Research Achievements	アルツハイマー博士の発見した神経原線維変化を構成するタウの凝集体形成はアルツハイマー病を引き起こす原因であると考えられているが、そのことを証明するためにはタウの凝集を阻害する物質がアルツハイマー病の認知機能低下を抑制することを示しなければならない。本研究で構築したタウ凝集のin vivoモデルとそれを用いた凝集阻害物質の同定はタウの凝集がアルツハイマー病の原因である証拠を示すための研究だけでなくアルツハイマー病の根本治療薬の開発に向けた第一歩である。