Abstract
In a mouse model of Parkinson's disease, new evidence shows that l-DOPA, which is used to treat the symptoms of the disease but also causes dyskinesia, results in a persistent activation of the protein kinase mTOR (mammalian target of rapamycin) in a subset of striatal medium spiny neurons. Moreover, blockade of a specific type of mTOR signaling (mTORC1) prevents the development of dyskinesia, but not the antiakinetic benefits produced by l-DOPA. Thus, mTORC1 may be a viable therapeutic target for dyskinesia caused by l-DOPA treatment in patients with Parkinson's disease.
MeSH terms
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Animals
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Antiparkinson Agents / metabolism
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Antiparkinson Agents / therapeutic use
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Carrier Proteins / metabolism
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Disease Models, Animal
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Humans
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Levodopa / metabolism
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Levodopa / therapeutic use
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Mechanistic Target of Rapamycin Complex 1
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Mice
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Multiprotein Complexes
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Parkinson Disease / drug therapy
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Parkinson Disease / metabolism*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Proteins
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Signal Transduction*
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TOR Serine-Threonine Kinases
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Transcription Factors / metabolism*
Substances
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Antiparkinson Agents
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Carrier Proteins
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Multiprotein Complexes
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Proteins
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Transcription Factors
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Levodopa
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Phosphotransferases (Alcohol Group Acceptor)
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MTOR protein, human
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mTOR protein, mouse
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Mechanistic Target of Rapamycin Complex 1
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TOR Serine-Threonine Kinases