Increasing evidence suggests that non-cell autonomous mechanisms contribute to the progression of neurodegenerative diseases such as Parkinson’s disease (PD). Mutations in the gene GBA1 are the strongest genetic risk for factor for developing PD, and also associated with faster disease progression. We used a fly model of GBA1 deficiency that has been previously characterized to have neurodegenerative phenotypes to investigate the role of GBA1 in a novel mechanism involving EVs in accelerating the propagation of pathogenic protein aggregates.

Investigate a potential role for GBA1 deficiency in accelerating the spread of protein aggregates via extracellular vesicles (EVs).

We previously developed a Drosophila model of GBA1 deficiency (GBA1^del) that manifests multiple phenotypes, including neurodegeneration and accelerated protein aggregation. We used a novel proteomic method using stable isotope labeling and mass spectrometry to measure global turnover rates and abundances in vivo in GBA1^del flies. We used standard Drosophila reagents, immunohistochemistry and Western blotting to evaluate protein aggregation. EV abundance was ascertained by nanoparticle tracking analysis.