Validating and Optimizing a Drosophila Larval Model of Parkinson's Synucleopathy

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with complex genetic and environmental underpinnings. Misexpression of human alpha-synuclein (αSyn) in Drosophila larval dopaminergic neurons has been shown to induce PD-like phenotypes, yet this model has not been fully optimized to assess different αSyn variants and their effects on various neuronal subtypes. By expanding the use of the Drosophila larval model, we demonstrate that dopaminergic neurons exhibit pronounced vulnerability to αSyn, particularly to E46K and A53T variants. Additionally, we show that vitamin C effectively mitigates locomotor impairments, highlighting oxidative stress as a key contributor to αSyn-induced dysfunction.