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 di...

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Vydáno v:NPJ Parkinson's Disease Ročník 10; číslo 1; s. 228 - 13
Hlavní autoři: Servillo, Federica, De Carluccio, Maria, Di Lazzaro, Giulia, Campanelli, Federica, Marino, Gioia, Natale, Giuseppina, Ledonne, Ada, Massaro Cenere, Mariangela, Paldino, Emanuela, Di Giuda, Daniela, Picca, Anna, Bove, Francesco, Di Iorio, Riccardo, Angeloni, Benedetta, Cimmino, Angelo Tiziano, Bellomo, Giovanni, Picconi, Barbara, Bentivoglio, Anna Rita, Mercuri, Nicola Biagio, Parnetti, Lucilla, Ghiglieri, Veronica, Viscomi, Maria Teresa, Calabresi, Paolo
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 30.11.2024
Nature Publishing Group
Nature Portfolio
Témata:
631/378/2591
692/617/375/1718
Animals
Biomedical and Life Sciences
Biomedicine
Denervation
Dopamine
Dyskinesia
Genotype & phenotype
Health risk assessment
Neurology
Neurosciences
Physiology
Risk factors
ISSN:2373-8057, 2373-8057
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:2373-8057
2373-8057
DOI:10.1038/s41531-024-00836-6