| Project/Area Number |
24591249
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
TAMAOKA Akira 筑波大学, 医学医療系, 教授 (50192183)
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| Co-Investigator(Kenkyū-buntansha) |
TAKUMA Hiroshi 筑波大学, 医学医療系, 講師 (00326258)
TOMIDOKORO Yasushi 筑波大学, 医学医療系, 講師 (80447250)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アルツハイマー病 / アミロイドβ蛋白 / ミトコンドリア / 酸化ストレス / BACE1 / γ-secretase / アミロイド前駆体蛋白（APP） / APP |
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| Outline of Final Research Achievements |
Mitochondrial dysfunction is implicated in the neurodegeneration in Alzheimer’s disease. Accumulation of amyloid β protein (Aβ) in mitochondria is suggested to be responsible for mitochondrial dysfunction. Then, we investigated processing of amyloid precursor protein (APP) in mitochondria in vitro studies.
Microsome and crude mitochondria fractions were obtained from human neuroblastoma SH-SY5Y cells overexpressing Swedish mutant APP by homogenization and centrifugation. By Western blot analysis. components of γ-secretase complex were similarly recovered in microsome and crude mitochondria fractions, and BACE1 was enriched in microsome fraction. After iodixanol gradient fractionation, γ-secretase complex components were recovered mainly in lysosome-enriched fractions. Taking these findings into consideration, it is unlikely that Aβ is generated from APP locally in mitochondria.
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