Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson's Disease

treatment with L-3,4-dihydroxyphenylalanine (L-Dopa) compensates for decreased striatal dopamine (DA) levels and reduces parkinson's disease (PD) symptoms. however, during disease progression, L-Dopa-induced dyskinesia (LID) develops virtually in all PD patients, making the control of PD symptoms difficult. thus, understanding the mechanisms underlying LID and the control of these motor abnormalities is a major issue in the care of PD patients. from experimental and clinical studies, a complex cascade of molecular and cellular events emerges, but the primary determinants of LID are still unclear. here, with a translational approach, including four animal models and a wide cohort of PD patients, we show that striatal DA denervation is the major causal factor for the emergence of LID, while alpha-synuclein aggregates do not seem to play a significant role. our data also support the concept that maladaptive basal ganglia plasticity is the main pathophysiological mechanism underlying LID.