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Development of synthetic Amyloid beta receptor for Alzheimer's disease therapy

Research Project

Project/Area Number 18K19525
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Hoshino Atsushi  京都府立医科大学, 医学(系)研究科(研究院), 助教 (50737210)

Co-Investigator(Kenkyū-buntansha) 伊東 恭子  京都府立医科大学, 医学(系)研究科(研究院), 教授 (80243301)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsアルツハイマー病 / 合成受容体 / バイオエンジニアリング / 合成アミロイドβ受容体 / アミロイドβ / 遺伝子治療
Outline of Final Research Achievements

We developed synthetic receptor that catch extracellular amyloid beta and degrade through endocytosis and lysosome pathway. We aimed to evaluate the therapeutic effect of this synthetic receptor in APP knock-in Alzheimer’s disease model mouse. The synthetic receptor was expressed in astrocyte, microglia, endothelial cells, and bone marrow cells. We have confirmed that adeno-associated virus injection in both side of hippocampus successfully expressed the synthetic receptor and reduced amyloid plaque and amyloid beta 40/42 content. We continue to examine the memory impairment and protective effect in transgene to other effector cells.

Academic Significance and Societal Importance of the Research Achievements

今回独自に考案した細胞外のものを取り込んで分解する合成受容体に関してアミロイドβにおいて分解能をマウスで証明することができた。この合成受容体は標的結合ドメインを置き換えることで色々なものを対象とできる。未発表だがApoBを標的としてLDLコレステロールを取り込み、LDL受容体欠損症に効果があることが分かっていたが、今回標的を変えても効果があることが確認された。またアルツハイマー病は現在治療方法の確立が最も求められている疾患の1つだが治療戦略の選択肢の一つになる可能性が示された。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report

URL: 

Published: 2018-07-25   Modified: 2021-02-19  

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