| Project/Area Number |
22590926
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KONO Satoshi 浜松医科大学, 医学部附属病院, 講師 (40397386)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 神経難病 / 鉄代謝 / 遺伝子発現 / 鉄 / 神経変性症 / 無セルロプラスミン血症 / フェロポルチン / アルツハイマー病 / βアミロイド前駆体蛋白質 / トランスフェリン / ミトコンドリア / 脂質代謝 / 脳内鉄蓄積症 / セラミド / ライソゾーム / セルロプラスミン / ヘプシジン / 肝細胞 / アストロサイト / 封入体 |
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| Research Abstract |
In 1987, we described the first case of aceruloplasminemia. This disease revealed an essential role for ceruloplasmin (Cp) in brain iron homeostasis. We now know that
(1) Cp regulates the efficiency of iron efflux
(2) Cp functions as a ferroxidase and regulates the oxidation of ferrous iron (Fe2+) to ferric iron (Fe3+)
(3) Cp does not bind to transferrin directly
(4) Cp stabilizes the cell surface iron transporter, ferroportin
and (5) glycophosphosinositide-linked Cp (GPI-Cp) is the predominant form expressed in the brain.In the brain, serum transferrin-bound iron is endocytosed by brain endothelial cells in a manner dependent on transferrin receptor 1, and iron is released into the brain interstitial fluid through ferroportin.Extracellular iron is oxidized by GPI -Cp, which is found in the foot processes of astrocytes, and then the iron binds to the transferrin synthesized by oligodendrocytes and is transported into neurons. β-amyloid precursor protein (APP) was found to possess ferroxidase activity like Cp, and to interact with neuron ferroportin. The brain needs several times the concentration of iron obtained from the blood to maintain its normal function. Taken together, the known functions of the iron metabolic molecules suggest the presence of a cycle of iron storage and reutilization within the brain.
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