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Table 2 LRRK2 as a therapeutic target for parkinsonism

From: The role of the LRRK2 gene in 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