TY - JOUR
T1 - Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson's Disease
AU - Servillo, Federica
AU - De Carluccio, Maria
AU - Di Lazzaro, Giulia
AU - Campanelli, Federica
AU - Marino, Gioia
AU - Natale, Giuseppina
AU - Ledonne, Ada
AU - Massaro Cenere, Mariangela
AU - Paldino, Emanuela
AU - Di Giuda, Daniela
AU - Picca, Anna
AU - Bove, Francesco
AU - Di Iorio, Riccardo
AU - Angeloni, Benedetta
AU - Cimmino, Angelo Tiziano
AU - Bellomo, Giovanni
AU - Picconi, Barbara
AU - Bentivoglio, Anna Rita
AU - Mercuri, Nicola Biagio
AU - Parnetti, Lucilla
AU - Ghiglieri, Veronica
AU - Viscomi, Maria Teresa
AU - Calabresi, Paolo
PY - 2024
Y1 - 2024
N2 - 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 α-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.
AB - 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 α-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.
KW - L-Dopa
KW - Parkinson's Disease
KW - dyskinesia
KW - L-Dopa
KW - Parkinson's Disease
KW - dyskinesia
UR - https://publicatt.unicatt.it/handle/10807/302063
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85211090037&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85211090037&origin=inward
U2 - 10.1038/s41531-024-00836-6
DO - 10.1038/s41531-024-00836-6
M3 - Article
SN - 2373-8057
VL - 10
SP - N/A-N/A
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
IS - 1
ER -