A Conserved Role for p48 Homologs in Protecting Dopaminergic Neurons from Oxidative Stress

• DOI: 10.1371/journal.pgen.1004718
• Publication Date: 2014-10-23T17:03:01Z
• Authors: Peter Bou Dib; Bettina Gnägi; Fiona Daly; Virginie Sabado; Damla Tas; Dominique A. Glauser; Peter Meister; Emi Nagoshi
• Keywords: Loss function

Parkinson's disease (PD) is the most common neurodegenerative movement disorder characterized by progressive loss of dopaminergic (DA) neurons. Both environmental and genetic factors are thought to contribute pathogenesis PD. Although several genes linked rare familial PD have been identified, endogenous risk for sporadic PD, which account majority cases, remain largely unknown. Genome-wide association studies identified many single nucleotide polymorphisms associated with in neurodevelopmental including transcription factor p48/ptf1a. Here we investigate whether p48 plays a role survival DA neurons Drosophila melanogaster Caenorhabditis elegans. We show that homolog, 48-related-2 (Fer2), expressed required development protocerebral anterior medial (PAM) cluster. Loss Fer2 expression adulthood causes PAM neuron degeneration aging flies along mitochondrial dysfunction elevated reactive oxygen species (ROS) production, leading locomotor deficits. The oxidative stress challenge upregulates exacerbates loss-of-function mutants. hlh-13, worm homolog p48, also Unlike fly counterpart, hlh-13 does not impair or under normal growth conditions. Yet, similar Fer2, upregulated upon an acute adult worms. Taken together, our results indicate homologs share protecting from degeneration, suggest worms provides novel tools study gene-environmental interactions affecting survival.