L-dopa induced dyskinesia in Parkinson's disease

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) is ultimately experienced by the vast majority of parkinsonian patients. Loss of dopamine in PD induces complex modifications in cellular signaling with numerous pathways showing altered responses to dopaminergic stimulation. Chronic L-dopa treatment further enhances the signaling alterations. The dopamine D1 receptor (D1R) signaling pathway has consistently been shown to be critically involved in LID genesis and manifestation in the striatum, the basal ganglia input structure. Interestingly, recent studies suggest an impact of structures outside of the basal ganglia in LID expression. The present attempts to provide an overview of our current understanding of LID pathophysiology.