Research on LRRK2 in Parkinson's disease has advanced, revealing how mutations activate the kinase, phosphorylate Rab proteins, disrupt cell functions like Hedgehog signaling, and contribute to the disease. LRRK2 inhibitors show promise for therapy.
Gain-of-function mutations in LRRK2 gene lead to by increasing phosphorylation of RAB GTPases. Over-phosphorylation of RAB3A disrupts synaptic vesicle transport in human neurons, altering synaptic protein distribution and likely contributing to PD.
This protocol describes the immunoblotting for components of the LRRK2 signalling pathway (LRRK2, LRRK2 pS935 and phospho-Rabs) using Invitrogen NuPage SDS-PAGE reagents and the BioRad Turbo Blot transfer system.