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Regulations on the brain iron cycle in the neurodegenerativedisorders

神经退行性疾病中脑铁循环的调节

基本信息

批准号：
22590926
负责人：
MIYAJIMA Hiroaki
金额：
$ 2.75万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

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, ferroportinand (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.

在1987年，我们描述了第一个病例的aceroplasminemia。这种疾病揭示了铜蓝蛋白（Cp）在脑铁稳态中的重要作用。我们现在知道（1）Cp调节铁流出的效率（2）Cp作为亚铁氧化酶起作用并调节亚铁（Fe 2+）氧化成三价铁（Fe 3+）（3）Cp不直接与转铁蛋白结合（4）Cp稳定细胞表面铁转运蛋白，ferroportinand（5）糖磷酸肌醇连接的Cp（GPI-Cp）是脑中表达的主要形式。血清转铁蛋白结合的铁以依赖于转铁蛋白受体1的方式被脑内皮细胞内吞，铁通过膜铁转运蛋白释放到脑间质液中。细胞外铁被星形胶质细胞足突中发现的GPI-Cp氧化，然后铁与少突胶质细胞合成的转铁蛋白结合并转运到神经元中。β-淀粉样前体蛋白（β-amyloid precursor protein，APP）具有与Cp类似的铁氧化酶活性，并与神经元铁转运蛋白（ferroportin）相互作用。大脑需要数倍于血液中铁的浓度来维持其正常功能。总的来说，铁代谢分子的已知功能表明脑内存在铁储存和再利用的循环。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Central diabetes insipidus and hypothalamic hypothyroidism associated with aceruloplasminemia.

中枢性尿崩症和下丘脑甲状腺功能减退症与铜蓝蛋白血症相关。

DOI：
10.2169/internalmedicine.49.3508
发表时间：
2010
期刊：
Internal medicine
影响因子：
1.2
作者：
Minemori Watanabe;Chikako Asai;Kota Ishikawa;Atsushi Kiyota;T. Terada;S. Kono;H. Miyajima;A. Okumura
通讯作者：
A. Okumura

Frontal lobe-medialed behavioral changes in amyotrophic lateral sclerosis : Are they independent of physical disabilities?

肌萎缩侧索硬化症中额叶介导的行为变化：它们与身体残疾无关吗？