Interaction between LRRK2 and GBA1

Here, we will examine the effect of inhibiting LRRK2 kinase activity on the lysosomal system by measuring the activity of beta-glucocerebrosidase (GCase). Loss-of-function mutations confer increased for PD and its enzymatic activity is closely linked to a-synuclein levels. We will use patient derived iPSC midbrain neurons that harbor GBA1 mutations to determine if small molecule inhibitors of LRRK2 can activate GCase and reduce a-synuclein.