VPS35 D620N Inhibits Autophagy by IGF-1R Dysregulation

Parkinson’s disease (PD) is the most common motor disease in the USA and results from loss of dopaminergic (DA) neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. Recently, a PD-causing mutation in VPS35 (D620N) was reported to block autophagy. Using overexpression and shRNA-mediated gene repression, our lab has discovered evidence supporting a role for altered signlaing by the Insulin-like Growth Factor-1 Receptor (IGF-1R), a receptor known to regulate autophagy, in VPS35 D620N-expressing cells. This work may lead to the identification of new targets for PD therapy.