Study Rationale:
Mutations in GBA, a gene that encodes an enzyme called glucocerebrosidase, are a common risk factor for Parkinson’s disease (PD). Inside cells, glucocerebrosidase must be escorted to the location where it will be active by LIMP-2, a membrane protein encoded by a gene called SCARB2. Genetic variants in SCARB2 have been associated with individuals with PD. However, the role that this gene might play in PD is unknown.
Hypothesis:
We hypothesize that genetic variants in the SCARB2 gene may affect the risk of PD and participate in the cellular mechanisms that are suspected or known to be involved in the disease.
Study Design:
To examine SCARB2’s association with PD, we will map the gene in a large-scale cohort of people with PD. Then, using a variety of human neuronal cell models, we will examine whether the variant forms of SCARB2 alter the toxic accumulation of alpha-synuclein, the activity of GBA, or the production of the LIMP-2 protein.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Because there are no effective treatments for PD that can stop or slow down the disease process, identifying new targets for drug development is crucial. Our study will determine whether SCARB2 might be a viable target for future therapeutic development.
Next Steps for Development:
If we can show that an increase or decrease in the activity of SCARB2 affects the cellular mechanisms potentially involved in PD, the next step would be to develop ways to correct SCARB2 activity as a potential therapeutic intervention.