Table 2.
LRRK2 as a therapeutic target for parkinsonism
| Model systems | Possible outcome | Clinical results | ||
|---|---|---|---|---|
| Kinase inhibitor | Staurosporine | both in vitro and in vivo | Inhibits LRRK2 autophosphorylation or LRRK2-mediated phosphorylation of myelin basic protein. Disrupts LRRK2 dimers. | - |
| Sunitinib | in vitro | Inhibits LRRK2-mediated phosphorylation of LRRKtide and Nictide. The LRRK2 A2016T mutant is resistant to this compound. | - | |
| H-1152 | in vitro | Inhibits LRRK2-mediated phosphorylation of LRRKtide and Nictide. The LRRK2 A2017T mutant is resistant to this compound. | - | |
| Indirubin-3’-monooxime | both in vitro and in vivo | Inhibits LRRK2 autophosphorylation and MBP and 4E-BP phosphorylation. | - | |
| Sorafenib | C. elegans and Drosophila models | Inhibits LRRK2 autophosphorylation and LRRK2-mediated MBP phosphorylation. | - | |
| GW5074 | C. elegans and Drosophila models | Inhibits LRRK2 autophosphorylation and MBP and 4E-BP phosphorylation. | - | |
| CZC-25146 | rodent model | Inhibits mutant LRRK2-mediated toxicity in primary rodent and human neurons. | - | |
| CZC-54252 | rodent model | Inhibits mutant LRRK2-mediated toxicity in human neurons. | - | |
| LRRK2-IN-1 | rodent model | Induces loss of 14-3-3 binding to LRRK2. Promotes dephosphorylation of Ser910 and Ser935 on LRRK2. | - | |
| GTPase modulator | ArfGAP1 | Drosophila model | Enhances both WT and mutant LRRK2 GTP hydrolysis. | - |
| Synthetic agent | diapocynin | rodent model | - | protect neurobehavioral function |