TAILIEUCHUNG - Báo cáo khoa học: Parkinson’s disease: Levodopa-induced dyskinesia and signal transduction

L-3,4-Dihydroxyphenylalanine (L-dopa) remains the most effective phar-macological treatment for relief of the severe motor impairments of Par-kinson’s disease. It is very effective in controlling parkinsonian symptoms in the initial phase of the disease, but its action wanes with time. Such ‘wearing-off’ imposes an escalation in the dosage of the drug, which ulti-mately fails to provide stable control of motor symptoms and results in the appearance of abnormal involuntary movements or dyskinesia | MINIREVIEW Parkinson s disease Levodopa-induced dyskinesia and signal transduction Emanuela Santini1 Emmanuel Valjent1 2 3 4 and Gilberto Fisone1 1 Department of Neuroscience Karolinska Institutet Stockholm Sweden 2 INSERM U839 Paris France 3 Universite Pierre et Marie Curie Paris France 4 Institut du Fer a Moulin Paris France Keywords 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine 6-hydroxydopamine cAMP-dependent protein kinase DA- and cAMP-regulated phosphoprotein of 32 kDa dopamine D1 receptor extracellular signal-regulated kinase immediate early genes medium spiny neurons phosphorylation striatum Correspondence E. Santini Department of Neuroscience Karolinska Institutet Retzius vag 8 171 77 Stockholm Sweden Fax 46 8 320899 Tel 46 8 524 83755 E-mail Received 23 October 2007 revised 21 December 2007 accepted 16 January 2008 doi L-3 4-Dihydroxyphenylalanine L-dopa remains the most effective pharmacological treatment for relief of the severe motor impairments of Parkinson s disease. It is very effective in controlling parkinsonian symptoms in the initial phase of the disease but its action wanes with time. Such wearing-off imposes an escalation in the dosage of the drug which ultimately fails to provide stable control of motor symptoms and results in the appearance of abnormal involuntary movements or dyskinesia. Peakdose L-dopa-induced dyskinesia LID currently represents one of the major challenges in the treatment of Parkinson s disease. Accumulating evidence suggests that LID derives from overstimulation of dopamine receptors located on the GABAergic medium spiny neurons MSNs of the dorsal striatum. These neurons form two distinct projection pathways which exert opposite effects on motor activity the direct striatonigral pathway promotes locomotion whereas the indirect striatopallidal pathway depresses locomotion. In order to understand the mechanisms underlying LID it is important to identify molecular .

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