Rescue of The PD-causing VPS35 Mutation (D620N) Using Autophagy-Activating Drugs

Parkinson’s disease (PD) is the most prevalent motor disease and second most common neurodegenerative disease in the USA. The motor features of PD result from the loss of dopaminergic neurons in the substantia nigra of the midbrain. It is believed that the autophagy dysfunction may underlie the loss of these important neurons. Recently, two separate groups reported that a mutation in Vacuolar Protein Sorting 35 (VPS35) is causal in a familial form of PD. We have evidence indicating that this mutation may cause PD through blockade of autophagy. To test this hypothesis, we are attempting to rescue the observed autophagy dysfunction by the PD-causing VPS35 mutation using drugs that activate autophagy in our cell culture model.