Thwarting dyskinesia by targeting mTORC1.
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.
Klann
Eric
E
Center for Neural Science, New York University, New York, NY 10003, USA. eklann@cns.nyu.edu
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007980:Levodopa / Q000378:metabolism / Q000627:therapeutic use; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011506:Proteins; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism*
D000978:Antiparkinson Agents; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D007980:Levodopa; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases