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| Content Provider | frontiers |
|---|---|
| Author | Cenci, M. Angela |
| Abstract | The dopamine 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 during the progression of PD, 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 dopamine transmission. Several presynaptic mechanisms converge to generate large dopamine 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 dopamine transmission depend on deficiency/dysfunction of the dopamine transporter, aberrant release of dopamine from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from dopamine) 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. |
| ISSN | 16642295 |
| DOI | 10.3389/fneur.2014.00242 |
| Volume Number | 5 |
| Journal | Frontiers in Neurology |
| Language | English |
| Publisher Date | 2014-12-15 |
| Access Restriction | Open |
| Subject Keyword | Neurovascular unit Neuropsychiatry Basal Ganglia Neuropharmacology Monoamines Movement Disorders Dystonia Neuroplasticity |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Neurology (clinical) |
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