L-DOPA therapy is well known to induce the side effect of dyskinesia in Parkinson’s disease patients. The biochemical pathways for this involve activation of rapamycin (mTOR) signaling in the striatum. The authors of this study found that Ras homolog enriched in striatum (Rhes), a striatal-specific protein, binds to and activates mTOR. Mice deficient in Rhes showed reduced striatal mTOR signaling and diminished dyskinesia. Since they maintained motor improvement on L-DOPA treatment, new drugs which bind to Rhes may prove useful in reducing side-effects in Parkinson patients receiving L-DOPA treatment.
Subramaniam S et al.: Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA–induced dyskinesia. Nature Neuroscience doi:10.1038/nn.2994 [Epub ahead of print December 18, 2011].