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Cenci MA. Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications. Front Neurol. 2014;5:242doi: 10.3389/fneur.2014.00242.
Cenci, M. A. (2014). Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications. Frontiers in neurology, 5242. https://doi.org/10.3389/fneur.2014.00242
Cenci, M Angela. "Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications." Frontiers in neurology vol. 5 (2014): 242. doi: https://doi.org/10.3389/fneur.2014.00242
Cenci MA. Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications. Front Neurol. 2014 Dec 15;5:242. doi: 10.3389/fneur.2014.00242. eCollection 2014. PMID: 25566170; PMCID: PMC4266027.
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Front Neurol. 2014 Dec 15;5:242. doi: 10.3389/fneur.2014.00242. eCollection 2014.

Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.

Frontiers in neurology

M Angela Cenci

Affiliations

  1. Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University , Lund , Sweden.

PMID: 25566170 PMCID: PMC4266027 DOI: 10.3389/fneur.2014.00242

Abstract

The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

Keywords: basal ganglia; dystonia; monoamines; movement disorders; neuropharmacology; neuroplasticity; neuropsychiatry; neurovascular unit

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