L-DOPA is an effective treatment for Parkinson’s disease (PD), but long-term therapy is associated with a progressive loss of motor control. Using the well-established mouse model of PD, in which the nigrostriatal pathway is selectively damaged by the toxin 6-hydroxydopamine, Santini et al. show that dyskinesia may develop as repeated administration of L-DOPA promotes mammalian target of rapamycin (mTOR) signaling through dopamine D1 receptor-mediated activation of the mTOR complex 1 (mTORC1). Mice with induced PD activated mTORC1 and exhibited dyskinesia when treated with L-DOPA alone. Similar mice treated with L-DOPA and rapamycin, which inhibits mTOR, benefited from the therapeutic action of L-DOPA and remained free of motor side effects. This indicates that rapamycin and other drugs that target the mTORC1 signaling cascade may warrant further investigation for their potential as anti-PD therapies.
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RESEARCH HIGHLIGHT| 02 September 2009
Neurodegenerative disease: preventing dyskinesia
Online ISSN: 1754-8411
Print ISSN: 1754-8403
Dis Model Mech (2009) 2 (9-10): 420.
Neurodegenerative disease: preventing dyskinesia. Dis Model Mech 2 September 2009; 2 (9-10): 420. doi:
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