Dopamine and Huntington's disease
(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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- author
- 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
- organization
- publishing date
- 2015-04
- 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
-
- pmid:25773746
- 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
- 2024-05-03 14:11:50
@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}},
keywords = {{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}},
doi = {{10.1586/14737175.2015.1025383}},
volume = {{15}},
year = {{2015}},
}