Abstract

Background

Alzheimer’s disease (AD) is one the most common types of dementia. Plaques of amyloid beta and neurofibrillary tangles of tau are two major hallmarks of AD. Metabolism of these two proteins, in part, depends on autophagy pathways. Autophagy dysfunction and protein aggregation in AD may be involved in a vicious circle. The aim of this study was to investigate whether tau or amyloid beta 42 (Aβ42) could affect expression of autophagy genes, and whether they exert their effects in the same way or not.

Methods

Expression levels of some autophagy genes, Hook, Atg6, Atg8, and Cathepsin D, were measured using quantitative PCR in transgenic Drosophila melanogaster expressing either Aβ42 or Tau R406W.

Results

We found that Hook mRNA levels were downregulated in Aβ42-expressing flies both 5 and 25 days old, while they were increased in 25-day-old flies expressing Tau R406W. Both Atg6 and Atg8 were upregulated at day 5 and then downregulated in 25-day-old flies expressing either Aβ42 or Tau R406W. Cathepsin D expression levels were significantly increased in 5-day-old flies expressing Tau R406W, while there was no significant change in the expression levels of this gene in 5-day-old flies expressing Aβ42. Expression levels of Cathepsin D were significantly decreased in 25-day-old transgenic flies expressing Tau R406W or Aβ42.

Conclusion

We conclude that both Aβ42 and Tau R406W may affect autophagy through dysregulation of autophagy genes. Interestingly, it seems that these pathological proteins exert their toxic effects on autophagy through different pathways and independently.

中文翻译：

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果蝇淀粉样病和 tau 蛋白病模型中自噬基因表达的显着改变。

摘要

背景

阿尔茨海默病 (AD) 是最常见的痴呆类型之一。β 淀粉样蛋白斑块和 tau 神经原纤维缠结是 AD 的两个主要标志。这两种蛋白质的代谢部分取决于自噬途径。AD中的自噬功能障碍和蛋白质聚集可能陷入恶性循环。本研究的目的是调查 tau 或淀粉样蛋白 42 (Aβ42) 是否会影响自噬基因的表达，以及它们是否以相同的方式发挥作用。

方法

使用定量 PCR 在表达 Aβ42 或 Tau R406W 的转基因黑腹果蝇中测量一些自噬基因Hook、Atg6、Atg8和组织蛋白酶 D 的表达水平。

结果

我们发现Hook mRNA 水平在 5 天和 25 天大的表达 Aβ42 的果蝇中下调，而在表达 Tau R406W 的 25 天大果蝇中则增加。无论ATG6和的Atg8在第5天进行了上调，然后将表达Aβ42或R406W头25日龄苍蝇下调。表达 Tau R406W 的 5 日龄果蝇的组织蛋白酶 D表达水平显着增加，而表达 Aβ42 的 5 日龄果蝇中该基因的表达水平没有显着变化。在表达 Tau R406W 或 Aβ42 的 25 日龄转基因果蝇中，组织蛋白酶 D 的表达水平显着降低。

结论

我们得出结论，Aβ42 和 Tau R406W 都可能通过自噬基因的失调来影响自噬。有趣的是，这些病理蛋白似乎通过不同的途径独立地对自噬发挥毒性作用。