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 <i>Drosophila</i> 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 <i>Drosophila</i> 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.