BMI SEMINAR // Transcriptional regulation of survival of dopaminergic neurons and its implication in Parkinson’s disease

Parkinson’s disease (PD) is the most common movement disorder characterized by the progressive loss of dopaminergic cells in the substantia nigra pars compacta. Accumulating evidence indicates that the interactions between genetic and environmental factors cause PD. Although several monogenic mutations linked to rare familial PD have been identified, other genetic determinants causative for sporadic PD, which account for more than 80% of cases, are largely unknown.
 
Our lab has recently shown that two transcription factor genes, Fer2 (p48 related-2) and dfoxo, play partly overlapping roles in the survival of a subclass DA neurons important for locomotion in flies. Loss-of-function of either gene causes cellular and behavioral phenotypes reminiscent of PD. Genetically, Fer2 and dfoxo act in parallel pathways to protect DA neurons from different stressors, but share common downstream processes leading to the regulation of mitochondrial biology and autophagy. These results add evidence to the complex gene-environment interactions underlying dopaminergic neurodegeneration and suggest that Fer2 and dfoxo mutants offer new tools to study pathogenesis of sporadic PD.