Rhes, a striatal–enriched small G–protein, mediates mTOR signaling and L–DOPA–induced dyskinesia

L–DOPA–induced dyskinesia, the rate–limiting side–effect in the therapy of Parkinson’s Disease, is mediated by activation of mTOR signaling in the striatum. We show that Rhes, a striatal–specific protein, binds to and activates mTOR. Moreover, Rhes deleted mice manifest reduced striatal mTOR signaling and diminished dyskinesia but maintain motor improvement upon L–DOPA treatment, implying therapeutic benefit for Rhes–binding drugs.