2002 Fiscal Year Final Research Report Summary
Cholesterol metabolism and Amyloid βprotein synthesis : Attention to Niemann-Pick discase type C
| Project/Area Number |
13670632
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Gunma University (2002)
The University of Tokyo (2001) |
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Principal Investigator |
YAMAZAKI Tsuneo Gunma University, Medicine, Assist. Prof, 医学部, 講師 (80200658)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Alzheimer's disease / Cholesterol / Niemann-Pick disease / Amyloid βprotein |
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| Research Abstract |
Amyloid β protein (Aβ) is a component of senile plaques, which are characteristic brain structures of Alzheimer's disease, and a putative causal molecule of the disease. Although the precise intracellular site of Aβ production is not known, cholesterol depletion strongly decreases the Aβ production in cultured cells. To investigate whether disturbance of intracellular cholesterol trafficking also affects the Aβ generation, we treated cultured cells with a compound which affects the cholesterol transport in late endosomes / lysosomes. These treatments caused cells to significantly accumulate Aβ, especially Aβ42 species, inside the cells. This accumulated Aβ was SDS insoluble but formic acid soluble, thus presumably an aggregated form. Cell fractionation studies revealed that the Aβ accumulated in the same fractions as free cholesterol. These results may indicate a strong interaction between free cholesterol and Aβ42 within the cell, and suggests that this particular metabolic pathway is responsible for intracellular accumulation of Aβ.
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