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Free radical production from betaAmyloid oligomers and mechanism of neurotoxicity deduced from them

β淀粉样蛋白寡聚物的自由基产生及其神经毒性机制

基本信息

批准号：
18591298
负责人：
HAYASHI Yoshihito
金额：
$ 2.23万
依托单位：
University of Miyazaki
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591298/
关键词：
beta amyloid free radical oligomer βアミロイドフリーラジカル凝集神経毒性

项目摘要

It is well known that beta amyloid (Aβ) peptides aggregate and make senile plaques up in AD patients' brain. So far the causes of AD is thought to be due to the excessive production of Aβ and its toxicity against neuronal cells in the brain in the process of aggregation. One of the main toxicities that Aβ shows against neuronal cells is due to productions of free radicals. It is thought that the stage when free radicals are produced maximally by Aβ is the very early period and it is just when Aβ changes into oligomers such as dimmer, timer and tetramer. This time we make oligomers (dimmer, trimmer, tetramer) using photocross-linking methods and separate them individually by using size gelchoromatography. Then we measured how much these oligomers produce H2O2 using APR solution and how many % of cells survive in the circumstances with Aβ oligomers. The results were that the molecular size of oligomers goes up there is tendency that the production of H2O2 is going up within 24 hours but there are no apparent differences between four forms of Aβ oligomers. The survive rate of the cells after 48hours about 60% cell were survived and there were also no apparent differences between Aβ oligomers. Therefore it will be needed that we should do further experiment using more bigger size oligomers such as tetramer, hexamer and soon carefully.

众所周知，β淀粉样蛋白（Aβ）肽在阿尔茨海默病患者的大脑中聚集并形成老年斑。迄今为止，AD的病因被认为是由于Aβ的过量产生及其在脑内聚集过程中对神经元细胞的毒性。Aβ对神经细胞的主要毒性之一是由于自由基的产生。认为Aβ产生自由基最多的阶段是极早期，正是Aβ转变为二聚体、计时器和四聚体等低聚物的阶段。这次我们用光交联的方法制备了低聚物（二聚体、三聚体、四聚体），并通过尺寸凝胶层析分离它们。然后我们测量了这些低聚物在APR溶液中产生H2O2的量，以及在Aβ低聚物的情况下有多少%的细胞存活。结果表明：Aβ低聚物的分子量逐渐增大，24 h内H2O2的产生量有增大的趋势，但4种形式的Aβ低聚物之间无明显差异。48h后细胞存活率约为60%，Aβ低聚物间无明显差异。因此，我们需要进一步的实验，使用更大尺寸的低聚物，如四聚体、六聚体等。