This dissertation investigates the role of alpha-synuclein in DNA double-strand break repair, specifically non-homologous end joining via CRISPR/Cas9 lentiviral and next generation sequencing approaches. It also contains novel findings of how Polo-like kinase family inhibition can lead to neuroprotection of cortical neurons bearing alpha-synuclein lewy pathology in a Parkinson's Disease mouse model using an in vivo imaging technique.