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Nat Neurosci. 2011 Dec 18;15(2):191-3. doi: 10.1038/nn.2994.

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

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  • 1The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

L-DOPA-induced dyskinesia, the rate-limiting side effect in the therapy of Parkinson's disease, is mediated by activation of mammalian target of rapamycin (mTOR) signaling in the striatum. We found that Ras homolog enriched in striatum (Rhes), a striatal-specific protein, binds to and activates mTOR. Moreover, Rhes(-/-) mice showed reduced striatal mTOR signaling and diminished dyskinesia, but maintained motor improvement on L-DOPA treatment, suggesting a therapeutic benefit for Rhes-binding drugs.

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PMID:
22179112
[PubMed - indexed for MEDLINE]
PMCID:
PMC3267880
Free PMC Article

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