| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
We have previously demonstrated that acyl-coA:cholesterol acyltransferase 1 (ACAT1) specific inhibitor K-604 reduced Amyloid β (Aβ) production and also suppressed the brain-specific oxysterol, 24S-hydroxycholesterol (24S-OHC)-induced neuronal cell death. In this study, we found that K-604 treatment inhibited Aβ production in a secretase substrate-specific manner. We also established the successful efficient delivery of a single dose of K-604 to the brain via the intranasal route. We further identified four long-chain unsaturated fatty acids with which 24S-OHC is esterified by ACAT. Accumulation of 24S-OHC esters affected the structure and function of endoplasmic reticulum, resulting in induction of neuronal cell death.
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