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

Srinivasa Subramaniam, Francesco Napolitano, Robert G. Mealer, Seyun Kim, Francesco Errico, Roxanne Barrow, Neelam Shahani, Richa Tyagi, Solomon H. Snyder, Alessandro Usiello

Research output: Contribution to journalArticle

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 Rhas -/- 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.

Original languageEnglish (US)
Pages (from-to)191-193
Number of pages3
JournalNature neuroscience
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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    Subramaniam, S., Napolitano, F., Mealer, R. G., Kim, S., Errico, F., Barrow, R., Shahani, N., Tyagi, R., Snyder, S. H., & Usiello, A. (2012). Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA-induced dyskinesia. Nature neuroscience, 15(2), 191-193. https://doi.org/10.1038/nn.2994