2012 Fiscal Year Final Research Report
Study for the mechanism linking intracellular amyloid precursor protein transport and cholesterol metabolism
| Project/Area Number |
23700428
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Doshisha University |
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Principal Investigator |
URANO Yasuomi 同志社大学, 生命医科学部, 助教 (22546674)
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| Project Period (FY) |
2011 – 2012
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| Keywords | アルツハイマー病 / 脂質代謝 / 酸化コレステロール / 細胞内輸送 |
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| Research Abstract |
A major pathological hallmark of Alzheimer’s disease is the accumulation of Amyloid ? (A?) in senile plaques. A? is generated from Amyloid precursor protein (APP). In this study, I found that the treatment with 24S-hydroxycholesterol, which is the brain-specific oxysterol, induced the expression of GRP78, an ER chaperone, through unfolded protein response pathways, and enhanced the formation of the APP/GRP78 complex. Thereby, 24S-hydroxycholesterol downregulates intracellular APP trafficking, resulting in the reduction of A? production.
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