Study Rationale: Mutations in PINK1 and Parkin genes underlie some forms of Parkinson’s disease (PD). The protein products of these genes are responsible for the maintenance and degradation of mitochondria, structures that produce energy for the cell. Neuronal health and function depend on the removal of damaged mitochondria, a process called mitophagy. We will study how PINK1 and Parkin carry out mitophagy to prevent brain cells from degenerating in PD. We already discovered one natural brake on the system, called Rubicon. By blocking Rubicon, we found we can make the system run better in cells, even when PINK1 and Parkin are missing in disease.
Hypothesis: We hypothesize that inhibiting Rubicon will enhance the process of mitophagy across the brain, providing a new disease-modifying therapy for PD.
Study Design: Understanding of the functioning of molecules in the brain is an incredibly complicated undertaking. We approach the problem by thinking of the brain as a network of cells, cells as a network of organelles, and organelles as a network of proteins and lipids. Our team includes experts on the organization of the brain, cells, organelles, proteins and lipids who collaborate to integrate all of these levels of understanding.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, compounds that inhibit Rubicon could represent a "disease-modifying" therapy that treat the causes of PD, rather than alleviating its symptoms. Such disease-modifying therapies could represent a cure for PD.
Next Steps for Development: These and other findings from our team have already been launched into drug discovery projects, and we are sure to discover several other drug targets in the coming years of the project.