Distinctive alteration in the expression of autophagy genes in Drosophila models of amyloidopathy and tauopathy.

IF 1.5 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Upsala journal of medical sciences Pub Date : 2020-11-01 Epub Date: 2020-07-11 DOI:10.1080/03009734.2020.1785063
Mehrnaz Haghi, Raheleh Masoudi, Seyed Morteza Najibi
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引用次数: 6

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.

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淀粉样变性和牛头病果蝇模型中自噬基因表达的显著改变。
背景:阿尔茨海默病(AD)是最常见的痴呆类型之一。淀粉样蛋白斑块和tau的神经原纤维缠结是AD的两个主要标志。这两种蛋白的代谢部分依赖于自噬途径。AD自噬功能障碍与蛋白聚集可能参与了一种恶性循环。本研究的目的是探讨tau或淀粉样蛋白β42 (a - β42)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:采用定量PCR方法检测Aβ42或Tau R406W转基因果蝇中自噬基因Hook、Atg6、Atg8和Cathepsin D的表达水平。结果:我们发现,在5日龄和25日龄表达a β42的果蝇中,Hook mRNA水平下调,而在25日龄表达Tau R406W的果蝇中,Hook mRNA水平升高。在表达Aβ42或Tau R406W的25日龄果蝇中,Atg6和at8均在第5天上调,然后下调。在表达Tau R406W的5日龄果蝇中,组织蛋白酶D的表达水平显著升高,而在表达Aβ42的5日龄果蝇中,该基因的表达水平无显著变化。在表达Tau R406W或a - β42的25日龄转基因果蝇中,组织蛋白酶D的表达水平显著降低。结论:Aβ42和Tau R406W均可能通过自噬基因失调影响自噬。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。
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来源期刊
Upsala journal of medical sciences
Upsala journal of medical sciences 医学-医学:内科
CiteScore
5.60
自引率
0.00%
发文量
31
审稿时长
6-12 weeks
期刊介绍: Upsala Journal of Medical Sciences is published for the Upsala Medical Society. It has been published since 1865 and is one of the oldest medical journals in Sweden. The journal publishes clinical and experimental original works in the medical field. Although focusing on regional issues, the journal always welcomes contributions from outside Sweden. Specially extended issues are published occasionally, dealing with special topics, congress proceedings and academic dissertations.
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