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The mechanism of cerebral accumulation of amyloid protein and aluminum.

淀粉样蛋白和铝的脑积累机制。

基本信息

批准号：
05670322
负责人：
TAGUCHI Tetsuya
金额：
$ 1.34万
依托单位：
Kochi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670322/
关键词：
amyloid lysosome macromolecules リソゾーム水迷路学習脳アミロイドアルミニウム

项目摘要

Alzheimer's disease is characterized by extracellular deposition in the brain of amyloid protein. The mechanism of accumulation of amyloid in brain is unknown and no simple model systems that produce extracellular amyloid have been reported. Here we speculate that the amyloid protein is generated from the degradation of amyloid precursor protein in cerebral lysosomes. To study the cellular mechanism of generation of the amyloid protein in the brain, pure and well characterized cerebral lysosomal fraction is needed. Therefore, we attempted to obtain a lysosomal fraction from rat brain which had a higher degree of purity in good yield using Percoll gradients following the swelling of mitochondria in the presence of calcium which would eliminate contamination from small amounts of mitochondria. Cerebral lysosomes were purified 330-fold with a yield of approximately 22%, which the highest reported for any cerebral lysosomal preparation. Burkart et al. (1982) have reported that brain lysosomes may play a major role not only in degrading macromolecules but also in their transport to the deposition site. Therefore, obtaining purified rat cerebral lysosomes should represent an important step in the study of the generation of macromolecules which accumulate in the brain and their secretion and/or transport.

阿尔茨海默氏病的特征在于淀粉样蛋白在脑中的细胞外沉积。淀粉样蛋白在脑中积累的机制尚不清楚，也没有简单的模型系统产生细胞外淀粉样蛋白的报道。我们推测淀粉样蛋白是由淀粉样前体蛋白在脑溶酶体中降解而产生的。为了研究淀粉样蛋白在脑中产生的细胞机制，需要纯的和充分表征的脑溶酶体组分。因此，我们试图从大鼠脑中获得一种溶酶体组分，该组分在钙存在下线粒体溶胀后使用Percoll梯度以良好的产率获得较高纯度，这将消除少量线粒体的污染。脑溶酶体纯化330倍，产率约为22%，这是任何脑溶酶体制备物中报道的最高产率。Burkart等人（1982年）报告称，脑溶酶体不仅在降解大分子方面发挥重要作用，而且在将大分子转运至沉积部位方面也发挥重要作用。因此，获得纯化的大鼠脑溶酶体应该代表在脑中积累的大分子的产生及其分泌和/或转运的研究中的重要步骤。