PMID- 22179112
OWN - NLM
STAT- MEDLINE
DCOM- 20120319
LR  - 20211203
IS  - 1546-1726 (Electronic)
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 15
IP  - 2
DP  - 2011 Dec 18
TI  - Rhes, a striatal-enriched small G protein, mediates mTOR signaling and 
      L-DOPA-induced dyskinesia.
PG  - 191-3
LID - 10.1038/nn.2994 [doi]
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 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.
FAU - Subramaniam, Srinivasa
AU  - Subramaniam S
AD  - The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Napolitano, Francesco
AU  - Napolitano F
FAU - Mealer, Robert G
AU  - Mealer RG
FAU - Kim, Seyun
AU  - Kim S
FAU - Errico, Francesco
AU  - Errico F
FAU - Barrow, Roxanne
AU  - Barrow R
FAU - Shahani, Neelam
AU  - Shahani N
FAU - Tyagi, Richa
AU  - Tyagi R
FAU - Snyder, Solomon H
AU  - Snyder SH
FAU - Usiello, Alessandro
AU  - Usiello A
LA  - eng
GR  - R01 MH018501/MH/NIMH NIH HHS/United States
GR  - R01 MH018501-43/MH/NIMH NIH HHS/United States
GR  - R37 MH018501/MH/NIMH NIH HHS/United States
GR  - MH18501/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111218
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adrenergic Agents)
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Immunosuppressive Agents)
RN  - 46627O600J (Levodopa)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.1.- (Rasd2 protein, mouse)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Mov Disord. 2012 Jun;27(7):815. PMID: 22912975
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Adrenergic Agents/toxicity
MH  - Animals
MH  - Antiparkinson Agents/adverse effects
MH  - Cell Line, Transformed
MH  - Corpus Striatum/drug effects/*metabolism/pathology
MH  - Culture Media, Serum-Free/pharmacology
MH  - Disability Evaluation
MH  - Disease Models, Animal
MH  - Dyskinesia, Drug-Induced/etiology/*pathology
MH  - Functional Laterality/drug effects/genetics
MH  - GTP-Binding Proteins/deficiency/*metabolism
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Levodopa/adverse effects
MH  - Mice
MH  - Mice, Knockout
MH  - Movement/drug effects
MH  - Mutation/genetics
MH  - Neurons/metabolism
MH  - Neurotoxicity Syndromes/drug therapy/etiology
MH  - Oxidopamine/toxicity
MH  - Phosphorylation/drug effects/genetics
MH  - Protein Binding/drug effects/genetics
MH  - Radioligand Assay
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction/genetics/*physiology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Time Factors
MH  - Transfection
PMC - PMC3267880
MID - NIHMS336322
EDAT- 2011/12/20 06:00
MHDA- 2012/03/20 06:00
PMCR- 2012/08/01
CRDT- 2011/12/20 06:00
PHST- 2011/08/08 00:00 [received]
PHST- 2011/10/26 00:00 [accepted]
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2012/03/20 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - nn.2994 [pii]
AID - 10.1038/nn.2994 [doi]
PST - epublish
SO  - Nat Neurosci. 2011 Dec 18;15(2):191-3. doi: 10.1038/nn.2994.