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Dopamine and Huntington's disease

Schwab, Laetitia C; Garas, Shady N; Garas, Shaady N; Drouin-Ouellet, Janelle LU ; Mason, Sarah L; Stott, Simon R LU and Barker, Roger A LU (2015) In Expert Review of Neurotherapeutics 15(4). p.58-445
Abstract

Huntington's disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA receptors. It is, therefore, not surprising that the drug treatments most commonly used in HD are anti-dopaminergic agents. Their use is based primarily on the belief that the characteristic motor impairments are a result of overactivation of the central dopaminergic pathways. While this is a useful starting place, it is clear that the behavior of the central dopaminergic pathways is not fully... (More)

Huntington's disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA receptors. It is, therefore, not surprising that the drug treatments most commonly used in HD are anti-dopaminergic agents. Their use is based primarily on the belief that the characteristic motor impairments are a result of overactivation of the central dopaminergic pathways. While this is a useful starting place, it is clear that the behavior of the central dopaminergic pathways is not fully understood in this condition and may change as a function of disease stage. In addition, how abnormalities in dopaminergic systems may underlie some of the non-motor features of HD has also been poorly investigated and this is especially important given the greater burden these place on the patients' and families' quality of life. In this review, we discuss what is known about central dopaminergic pathways in HD and how this informs us about the mechanisms of action of the dopaminergic therapies used to treat it. By doing so, we will highlight some of the paradoxes that exist and how solving them may reveal new insights for improved treatment of this currently incurable condition, including the possibility that such drugs may even have effects on disease progression and pathogenesis.

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Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Dopamine, Humans, Huntington Disease, Receptors, Dopamine, Journal Article, Review
in
Expert Review of Neurotherapeutics
volume
15
issue
4
pages
14 pages
publisher
Future Drugs Ltd
external identifiers
  • scopus:84925866890
ISSN
1744-8360
DOI
10.1586/14737175.2015.1025383
language
English
LU publication?
no
id
5ecba6c9-062f-4019-ac75-0e1c1686e4cb
date added to LUP
2016-11-22 08:59:11
date last changed
2017-11-12 04:26:19
@article{5ecba6c9-062f-4019-ac75-0e1c1686e4cb,
  abstract     = {<p>Huntington's disease (HD) is an incurable, inherited, progressive neurodegenerative disorder that is defined by a combination of motor, cognitive and psychiatric features. Pre-clinical and clinical studies have demonstrated an important role for the dopamine (DA) system in HD with dopaminergic dysfunction at the level of both DA release and DA receptors. It is, therefore, not surprising that the drug treatments most commonly used in HD are anti-dopaminergic agents. Their use is based primarily on the belief that the characteristic motor impairments are a result of overactivation of the central dopaminergic pathways. While this is a useful starting place, it is clear that the behavior of the central dopaminergic pathways is not fully understood in this condition and may change as a function of disease stage. In addition, how abnormalities in dopaminergic systems may underlie some of the non-motor features of HD has also been poorly investigated and this is especially important given the greater burden these place on the patients' and families' quality of life. In this review, we discuss what is known about central dopaminergic pathways in HD and how this informs us about the mechanisms of action of the dopaminergic therapies used to treat it. By doing so, we will highlight some of the paradoxes that exist and how solving them may reveal new insights for improved treatment of this currently incurable condition, including the possibility that such drugs may even have effects on disease progression and pathogenesis.</p>},
  author       = {Schwab, Laetitia C and Garas, Shady N and Garas, Shaady N and Drouin-Ouellet, Janelle and Mason, Sarah L and Stott, Simon R and Barker, Roger A},
  issn         = {1744-8360},
  keyword      = {Animals,Dopamine,Humans,Huntington Disease,Receptors, Dopamine,Journal Article,Review},
  language     = {eng},
  number       = {4},
  pages        = {58--445},
  publisher    = {Future Drugs Ltd},
  series       = {Expert Review of Neurotherapeutics},
  title        = {Dopamine and Huntington's disease},
  url          = {http://dx.doi.org/10.1586/14737175.2015.1025383},
  volume       = {15},
  year         = {2015},
}