Rab GTPase phosphorylation in Parkinson’s Disease

Suzanne Pfeffer

Stanford University, Department of Biochemistry, Beckman Center, Room B413, 279 Campus Drive, Stanford, CA 94305-5307, USA, pfeffer@stanford.edu

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases and activating mutations in LRRK2 are a common cause of Parkinson’s. Loss of function mutations in glucocerebrosidase (GBA1) are also linked to this disease.  We have shown that both LRRK2 pathway and GBA1 mutations may cause Parkinson's by a convergent pathway--loss of Hedgehog signaling. Remarkably, treatment of mice with a LRRK2 inhibitor restores cilia and rescues neuroprotective factor production, which is great news for patients.

Go back