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Updated: Sep 16, 2025
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
A Drosophila model of prion disease and its metabolic changes in the brain
Dongdong Wang1, Zhixin Sun1, Pei Wen1
1National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Background:
Prion diseases (PrDs) are fatal transmissible neurodegenerative disorders caused by misfolded prion protein, which is highly expressed in the brain. Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.
Methods:
Drosophila transgenic for hamster prion protein (HaPrP) was generated by Valium20 transformation. Locomotion, longevity, protease resistance, and histology were assessed, and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.
Results:
The Drosophila model exhibited pan-neuronal expression of HaPrP, with expression levels increasing with age. Flies displayed reduced climbing ability, shortened lifespan, and vacuolar structures in the brain. Additionally, HaPrP expressed in older flies demonstrated resistance to digestion by 5 μg/mL Proteinase K. The Drosophila model also displayed alterations in protein, lipid, and carbohydrate metabolism. We hypothesize that glutamate, N-acetylaspartate, ceramide, phosphatidylethanolamine, dihydroxyacetone phosphate, ribose-5-phosphate, and pyruvate are key metabolites potentially related to PrDs. Metformin improved locomotor activity, reduced PrPres formation, and ameliorated mitochondrial dysfunction in flies, which may be associated with alterations in succinate, pyruvate, choline, and sphingomyelin levels.
Conclusions:
We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals. Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the high-throughput screening of potential therapeutic compounds.
