Expanding the repertoire of L-DOPA's actions: A comprehensive review of its functional neurochemistry

Progress in Neurobiology
P De DeurwaerdèreMark J Millan

Abstract

Though a multi-facetted disorder, Parkinson's disease is prototypically characterized by neurodegeneration of nigrostriatal dopaminergic neurons of the substantia nigra pars compacta, leading to a severe disruption of motor function. Accordingly, L-DOPA, the metabolic precursor of dopamine (DA), is well-established as a treatment for the motor deficits of Parkinson's disease despite long-term complications such as dyskinesia and psychiatric side-effects. Paradoxically, however, despite the traditional assumption that L-DOPA is transformed in residual striatal dopaminergic neurons into DA, the mechanism of action of L-DOPA is neither simple nor entirely clear. Herein, focussing on its influence upon extracellular DA and other neuromodulators in intact animals and experimental models of Parkinson's disease, we highlight effects other than striatal generation of DA in the functional profile of L-DOPA. While not excluding a minor role for glial cells, L-DOPA is principally transformed into DA in neurons yet, interestingly, with a more important role for serotonergic than dopaminergic projections. Moreover, in addition to the striatum, L-DOPA evokes marked increases in extracellular DA in frontal cortex, nucleus accumbens, the subth...Continue Reading

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Citations

Dec 16, 2016·ACS Chemical Neuroscience·Philippe De DeurwaerdèreJosé Marco-Contelles
Mar 6, 2017·Progress in Neurobiology·Philippe De DeurwaerdèreGiuseppe Di Giovanni
May 2, 2017·ACS Chemical Neuroscience·Philippe HuotAndrew C McCreary
May 26, 2017·Expert Opinion on Investigational Drugs·Silvia CerriFabio Blandini
Feb 6, 2017·Journal of Neuroscience Methods·Françoise Dellu-HagedornPhilippe De Deurwaerdère
Jun 20, 2017·Journal of Neurochemistry·Jesper F HavelundJan Bert Gramsbergen
Apr 18, 2018·Macromolecular Bioscience·Georgina FabregatCarlos Alemán
Feb 9, 2018·Journal of Neural Transmission·Oscar Solís, Rosario Moratalla
Jun 21, 2018·The European Journal of Neuroscience·Tanuja Bordia, Xiomara A Perez
Aug 18, 2018·The European Journal of Neuroscience·Emma L Lane
Oct 26, 2018·Developmental Neurobiology·Lisa C HiuraAlexander G Ophir
Jul 25, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Laura BoiAnna R Carta
Jan 8, 2020·International Journal of Molecular Sciences·Abdeslam ChagraouiPhilippe De Deurwaerdère
May 24, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Dhruv PatelKalipada Pahan
Sep 29, 2017·Frontiers in Cellular Neuroscience·Cristina MiguelezPhilippe De Deurwaerdère
May 15, 2018·Movement Disorders Clinical Practice·Jared Thomas HinkleGregory M Pontone
Sep 15, 2018·Frontiers in Neuroscience·Fatemeh N Emamzadeh, Andrei Surguchov
Apr 24, 2020·Frontiers in Pharmacology·Elena Paredes-RodriguezCristina Miguelez
Sep 28, 2018·Molecular Neurobiology·José-Rubén García-MontesRosario Moratalla
Jun 27, 2020·Fortschritte der Neurologie-Psychiatrie·Dirk WoitallaUllrich Wüllner
Dec 10, 2016·Frontiers in Neuroscience·Giuseppe Di GiovanniPhilippe De Deurwaerdère
Aug 23, 2019·Biomolecules·Claudia CarrariniLaura Bonanni
Jan 3, 2021·Brain Research Bulletin·Cheng-Lu ZhangYu-He Yuan
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Feb 25, 2021·Signal Transduction and Targeted Therapy·Yan WangJian-Dong Jiang
Jan 28, 2019·Neurochemistry International·Abdeslam ChagraouiPhilippe De Deurwaerdère
Jun 21, 2017·Trends in Pharmacological Sciences·Lina Leinartaité, Per Svenningsson
Jul 25, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ahmed M ShehataLamberto Re
Aug 20, 2021·The Journal of Physiology·Marie BoulainLaurent Juvin

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