Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease
Abstract 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 sy...
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| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-024-00836-6 |
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| author | Federica Servillo Maria De Carluccio Giulia Di Lazzaro Federica Campanelli Gioia Marino Giuseppina Natale Ada Ledonne Mariangela Massaro Cenere Emanuela Paldino Daniela Di Giuda Anna Picca Francesco Bove Riccardo Di Iorio Benedetta Angeloni Angelo Tiziano Cimmino Giovanni Bellomo Barbara Picconi Anna Rita Bentivoglio Nicola Biagio Mercuri Lucilla Parnetti Veronica Ghiglieri Maria Teresa Viscomi Paolo Calabresi |
| author_facet | Federica Servillo Maria De Carluccio Giulia Di Lazzaro Federica Campanelli Gioia Marino Giuseppina Natale Ada Ledonne Mariangela Massaro Cenere Emanuela Paldino Daniela Di Giuda Anna Picca Francesco Bove Riccardo Di Iorio Benedetta Angeloni Angelo Tiziano Cimmino Giovanni Bellomo Barbara Picconi Anna Rita Bentivoglio Nicola Biagio Mercuri Lucilla Parnetti Veronica Ghiglieri Maria Teresa Viscomi Paolo Calabresi |
| author_sort | Federica Servillo |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-15139aaebfe7489f9dcd055e7b51e20c |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-15139aaebfe7489f9dcd055e7b51e20c2024-12-01T12:15:04ZengNature Portfolionpj Parkinson's Disease2373-80572024-11-0110111310.1038/s41531-024-00836-6Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s DiseaseFederica Servillo0Maria De Carluccio1Giulia Di Lazzaro2Federica Campanelli3Gioia Marino4Giuseppina Natale5Ada Ledonne6Mariangela Massaro Cenere7Emanuela Paldino8Daniela Di Giuda9Anna Picca10Francesco Bove11Riccardo Di Iorio12Benedetta Angeloni13Angelo Tiziano Cimmino14Giovanni Bellomo15Barbara Picconi16Anna Rita Bentivoglio17Nicola Biagio Mercuri18Lucilla Parnetti19Veronica Ghiglieri20Maria Teresa Viscomi21Paolo Calabresi22Neurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeuroscienze Sperimentali, IRCCS Fondazione Santa LuciaNeuroscienze Sperimentali, IRCCS Fondazione Santa LuciaNeuroscienze Sperimentali, IRCCS Fondazione Santa LuciaMedicina Nucleare, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSLaboratorio di Neurochimica Clinica, Neurologia, Dipartimento di Medicina, Università degli Studi di PerugiaDipartimento di Scienze Umane e Promozione della Qualità della Vita, Università Telematica San RaffaeleNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeuroscienze Sperimentali, IRCCS Fondazione Santa LuciaLaboratorio di Neurochimica Clinica, Neurologia, Dipartimento di Medicina, Università degli Studi di PerugiaNeurologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCSNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreNeurologia, Dipartimento di Neuroscienze, Università Cattolica del Sacro CuoreAbstract 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.https://doi.org/10.1038/s41531-024-00836-6 |
| spellingShingle | Federica Servillo Maria De Carluccio Giulia Di Lazzaro Federica Campanelli Gioia Marino Giuseppina Natale Ada Ledonne Mariangela Massaro Cenere Emanuela Paldino Daniela Di Giuda Anna Picca Francesco Bove Riccardo Di Iorio Benedetta Angeloni Angelo Tiziano Cimmino Giovanni Bellomo Barbara Picconi Anna Rita Bentivoglio Nicola Biagio Mercuri Lucilla Parnetti Veronica Ghiglieri Maria Teresa Viscomi Paolo Calabresi Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease npj Parkinson's Disease |
| title | Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease |
| title_full | Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease |
| title_fullStr | Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease |
| title_full_unstemmed | Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease |
| title_short | Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson’s Disease |
| title_sort | molecular and cellular determinants of l dopa induced dyskinesia in parkinson s disease |
| url | https://doi.org/10.1038/s41531-024-00836-6 |
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