The degeneration of dopaminergic neurons is characteristic of Parkinson's disease (PD). Previous studies using Drosophila models of PD have been helpful in identifying the cellular and molecular mechanisms responsible for the loss of dopaminergic neurons, but little is known about how these neurons become selectively vulnerable to the development of PD. Now, Daniel Babcock and colleagues (Cunningham et al., 2018) describe the progressive loss of dopaminergic neurons in scarlet mutants. The authors identify scarlet as a target following an unbiased screen to identify novel genes associated with degeneration of dopaminergic neurons. They show that scarlet mutants have locomotor defects and a shortened lifespan, and the loss of dopaminergic neurons in these mutants is cell autonomous. The neurodegeneration observed in the scarlet mutants can be modified genetically and pharmacologically by manipulating metabolite levels in the kynurenine pathway. Finally, the authors demonstrate a neuroprotective role for scarlet by showing that its expression can rescue α-synuclein-mediated toxicity in a model of PD. Taken together, these results reveal not only a new function for the well-known scarlet mutation, but also a new neuroprotective mechanism in a model of PD.
