Alteration of Drp1 Expression in Drosophila Models of Parkinson Disease

Autor: Brian Ernest Staveley, Azra Hasan
Rok vydání: 2020
Předmět:
DOI: 10.21203/rs.3.rs-39652/v1
Popis: Background: Parkinson Disease (PD) and other neurodegenerative diseases have a significant relationship with mitochondrial dysfunction. The substantial effect of mitochondrial dynamics in PD has led us to study the role of the gene encoding the mitochondrial fission protein Drp1 in Drosophila models. Drp1 is a member of the highly conserved, dynamin family of protein encoding genes. Drp1 plays an essential role in the maintenance of the mitochondrial, peroxisomal, and endoplasmic reticulum (ER) dynamics, and has been found to regulate processes during homeostasis and cell survival.Results: The directed expression of Drp1 in Drosophila melanogaster neurons under the control of the Ddc-Gal4 transgene decreases the lifespan and compromises climbing ability over time. The directed inhibition of Drp1 produces a novel model of Parkinson Disease, as this causes little change in mean lifespan but a significant decrease in locomotor or climbing abilities. Interestingly, the loss of park dependent Drosophila model of PD is rescued by the directed inhibition of Drp1.Conclusion: The compromised climbing abilities in flies with directed inhibition of Drp1 has produced a new model for Parkinson Disease and can be used to further investigate the mechanism(s) underlying PD and other neurodegenerative diseases. Interestingly, the combined inhibition of both Drp1 and park suppresses Parkinson Disease phenotypes and promotes survival.
Databáze: OpenAIRE