Modeling Parkinson's Disease in a Petri Dish: Dopaminergic Neurons Derived from Stem Cells Challenged with Lewy Body Protein á-synuclein

Parkinson’s disease (PD) affects 1% of the population over the age of 60. It is a neurodegenerative disorder that specifically affects A9 dopaminergic (DA) neurons and spares adjacent A10 DA neurons. A major causative factor for neurodegeneration in PD is the overexpression of a-synuclein, a protein abundant in Lewy bodies that are pathogenomonic for the disease. We hypothesize that A9 derived neurons will be more vulnerable to extracellular a-synuclein compared to A10 neurons. We are generating a novel PD model by taking mouse tail fibroblasts and transfecting them with the four proteins using a retroviral system. This approach enables us to “rejuvenate” the cells and turn them into pluripotent stem cells (iPSCs). We then use an established five-stage protocol for dopaminergic differentiation via embryoid body differentiation and neuroprecursor selection using magnetic beads cell sorting with the neural cell adhesion molecule (NCAM). We have derived mature neurons from our control iPS line and are selecting for neuroprecursors in our PD iPSC line. Challenging with α-synuclein protein and subsequent immunostaining will illuminate viability of A9 and A10 neurons. This novel model of PD could lay the foundation for novel drug discovery approaches and it could also become a powerful tool to test environmental risk factors like pesticides on DA neurons in a petri dish.