The role of glia and CED-1/MEGF10 in C. elegans models of Parkinson's disease

Abstract

Parkinson's disease (PD) is marked by progressive dopamine neuron degeneration, but the phagocytic receptors and cells that clear dopamine neuron corpses are unknown. Further, while other cell types like glia, skin, and muscle are also affected in PD, their role in disease progression is unclear. In my thesis project, I found that astrocyte-like CEPsh glia are neurotoxic in C. elegans PD models by regulating the neuronal dopamine biosynthesis enzyme CAT-2/tyrosine hydroxylase. I also identified epithelia and muscle as the phagocytes for dopamine neuron corpses. They engulf by recognizing phosphatidylserine on necrotic-like neuron corpses via the conserved receptor CED-1/Draper/MEGF10. Loss of ced-1 protects from loss of dopamine neurons but does not protect against the impairment of associated dopaminergic behaviors. Altogether, my thesis work provides evidence for the involvement of glia, muscle, and epithelial cells as potential mediators of dopamine neuron degeneration. Thus, my thesis work suggests that PD may be a disease of multi-organ dysfunction and could inform future therapeutic interventions.