TY - JOUR
T1 - Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA-induced dyskinesia
AU - Subramaniam, Srinivasa
AU - Napolitano, Francesco
AU - Mealer, Robert G.
AU - Kim, Seyun
AU - Errico, Francesco
AU - Barrow, Roxanne
AU - Shahani, Neelam
AU - Tyagi, Richa
AU - Snyder, Solomon H.
AU - Usiello, Alessandro
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856281757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856281757&partnerID=8YFLogxK
U2 - 10.1038/nn.2994
DO - 10.1038/nn.2994
M3 - Article
C2 - 22179112
AN - SCOPUS:84856281757
VL - 15
SP - 191
EP - 193
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 2
ER -