Study Rationale: Mutations in the PLA2G6 gene lead to neurodegeneration linked to Parkinson’s disease (PD), but the mechanism is unknown. The gene encodes an enzyme that breaks down the lipid molecules that form cell membranes. We have engineered a preclinical model expressing a human PD-linked mutation in PLA2G6. We will analzye this model to discover the key cellular pathways that are disrupted in the brain by the PLA2G6 mutation.
Hypothesis: We hypothesize that study of this preclinical model could uncover new mechanisms and cellular pathways that leads to PD.
Study Design: We have engineered a preclinical model expressing a human PD-linked mutation in PLA2G6. We will analyze this model to discover the key cellular pathways that are disrupted in the brain by the PLA2G6 mutation. We will assess whether the mutation leads to disturbed movement and nervous system pathology similar to that seen in people with PD. We will investigate whether PLA2G6 interacts with other PD gene pathways. We will finally determine the effect of the PLA2G6 mutation on the cell structures that make energy (mitochondria) or remove waste (lysosomes).
Impact on Diagnosis/Treatment of Parkinson’s disease: Discovering new mechanisms and cellular pathways may lead to new ideas for diagnosis and treatment of PD.
Next Steps for Development: Discoveries from studies of this preclinical model will be tested in people with PLA2G6 mutation to confirm whether the findings apply to humans and could lead to new clinical biomarkers for PD.