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

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.

Keywords:

• Alzheimer’s disease
• amyloid beta
• autophagy genes
• Drosophila melanogaster
• tau

Acknowledgements

We would like to show our gratitude and appreciation to Dr. M. Haddadi for providing the desired Drosophila stock and sharing his pearls of wisdom with us during the course of working with the flies. We also express our sincere thanks to Dr M. Ebrahimi for assistance with FLEYE plugin.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Notes on contributors

Mehrnaz Haghi, PhD student of Molecular and Cellular Biology, Department of Biology, Shiraz University, Shiraz, Iran.

Raheleh Masoudi, PhD of Molecular Genetics, Assistant professor in Department of Biology, Shiraz University, Shiraz, Iran.

Seyed Morteza Najibi, PhD of Statistics, Researcher at Center for Molecular Protein Science, Lund University, Lund, 22362, Sweden.

Additional information

Funding

This research was financially supported by Shiraz University Research Council. Seyed Morteza Najibi was supported by a Swedish Research Council grant (2016–06947) and a grant from eSSENCE@LU.