Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.
Cenci Nilsson, Angela LU
(2014)
In Frontiers in Neurology
5.
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5040990
- author
- Cenci Nilsson, Angela
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Frontiers in Neurology
- volume
- 5
- article number
- 242
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:25566170
- scopus:84910617976
- pmid:25566170
- wos:000209629300228
- ISSN
- 1664-2295
- DOI
- 10.3389/fneur.2014.00242
- language
- English
- LU publication?
- yes
- id
- 72c4cccb-815a-4eeb-895d-f3ec0c876bc7 (old id 5040990)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25566170?dopt=Abstract
- date added to LUP
- 2016-04-01 13:42:12
- date last changed
- 2022-04-06 06:33:23
@article{72c4cccb-815a-4eeb-895d-f3ec0c876bc7,
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.}},
author = {{Cenci Nilsson, Angela}},
issn = {{1664-2295}},
language = {{eng}},
publisher = {{Frontiers Media S. A.}},
series = {{Frontiers in Neurology}},
title = {{Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.}},
url = {{https://lup.lub.lu.se/search/files/3540702/7753805}},
doi = {{10.3389/fneur.2014.00242}},
volume = {{5}},
year = {{2014}},
}