Analysis of Alzheimer's disease induced by abnormal cholesterol metabolism

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K21317
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics; General pharmacology
• Research Institution: Jichi 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
• Keywords: アルツハイマー / アミロイドβ / オキシステロール / 24S-HC

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.

Free Research Field

内分泌代謝

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。