Fig. 4: Hypothesis for extracellular and cellular LRRK2 inhibition.

Diagram illustrating a hypothetical relationship of LRRK2 protein in tissue or biofluids (i.e., in exosomes), with %ATP-bound LRRK2 with increasing concentrations of ATP-competitive small-molecule LRRK2 kinase inhibitors. In the model, exosome depletion of LRRK2 occurs initially without lowering tissue levels of total LRRK2 is shown in yellow. The green area highlights higher concentrations of drug and the corresponding loss of any ATP-bound LRRK2, resulting in the depletion of LRRK2 protein in both exosomes and tissues.