Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model

PLoS One. 2017 May 22;12(5):e0176183. doi: 10.1371/journal.pone.0176183. eCollection 2017.

Abstract

Background: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila.

Methods: Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC).

Results: Exogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration.

Conclusion: The protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / genetics*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Animals, Genetically Modified
  • Brain / metabolism*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Disease Models, Animal
  • Drosophila / genetics*
  • Drosophila / physiology
  • Female
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Male
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Mitochondrial Dynamics
  • Peptide Fragments / genetics*
  • Peptide Fragments / metabolism

Substances

  • Amyloid beta-Peptides
  • Cytoskeletal Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Adenosine Triphosphate
  • DRP1 protein, Drosophila
  • GTP-Binding Proteins

Grants and funding

We received no specific funding for this study.