Thwarting dyskinesia by targeting mTORC1

Sci Signal. 2009 Jul 21;2(80):pe42. doi: 10.1126/scisignal.280pe42.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiparkinson Agents / metabolism
  • Antiparkinson Agents / therapeutic use
  • Carrier Proteins / metabolism
  • Disease Models, Animal
  • Humans
  • Levodopa / metabolism
  • Levodopa / therapeutic use
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Proteins
  • Signal Transduction*
  • TOR Serine-Threonine Kinases
  • Transcription Factors / metabolism*

Substances

  • Antiparkinson Agents
  • Carrier Proteins
  • Multiprotein Complexes
  • Proteins
  • Transcription Factors
  • Levodopa
  • Phosphotransferases (Alcohol Group Acceptor)
  • MTOR protein, human
  • mTOR protein, mouse
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases