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Analysis of Alzheimer's disease induced by abnormal cholesterol metabolism

Research Project

Project/Area Number 16K21317
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
General pharmacology
Research InstitutionJichi Medical University

Principal Investigator

YAMAMURO DAISUKE  自治医科大学, 医学部, リサーチ・レジデント (20739255)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアルツハイマー / アミロイドβ / オキシステロール / 24S-HC / Aβ / 24S-ヒドロキシコレステロール / アルツハイマー型認知症 / NCEH1 / ACAT1 / NCEH1阻害剤 / ACAT1阻害剤 / 脂質代謝異常
Outline of Final Research Achievements

In this study, we examined whether NCEH1 is involved in Alzheimer’s disease (AD) development such as amyloidβ(Aβ) deposition by regulating brain CE and 24S-HC levels from both in vitro and in vivo experiments. As a result, the relationship between NCEH1 and AD was not demonstrated at in vitro experiments. In vivo experiments suggested that the accumulation of CE and 24S-HC ester induced NCEH1 deficiency was caused Aβ deposition (which is the risk factor of AD) and memory impairment. In the future,it can be expected to lead to the discovery of new AD risk factors and the presentation of new drug targets by elucidating the mechanism of Aβ deposition induced by CE and 24S-HC ester accumulation.

Academic Significance and Societal Importance of the Research Achievements

本研究により、in vivo レベルでのNCEH1欠損によるester体蓄積がアルツハイマー疾患発症の原因因子であるAβ沈着さらには記憶障害へと関連することが動物実験から示唆された。脂質代謝酵素とAD発症との関連研究はまだ未開拓な領域であり、CE水解活性を触媒するNCEH1に着目した研究報告はないことから、本研究成果をさらに発展させることができれば、新たなアルツハイマー発症因子の発見、さらにはアルツハイマー疾患治療薬へと成り得る創薬ターゲットの提示に繋がることが期待できる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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