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rdf:type |
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lifeskim:mentions |
umls-concept:C0003069,
umls-concept:C0020179,
umls-concept:C0026336,
umls-concept:C0026339,
umls-concept:C0038590,
umls-concept:C0041491,
umls-concept:C0086418,
umls-concept:C0178539,
umls-concept:C0876934,
umls-concept:C0936012,
umls-concept:C1515926
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pubmed:issue |
1
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pubmed:dateCreated |
2003-11-4
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pubmed:abstractText |
Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder that is pathologically characterized by a striatal-specific degeneration. Aberrant dopamine neurotransmission has been proposed as a mechanism underlying the movement disorder of HD. We report that the enzymatic activity of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine biosynthesis, is decreased in a transgenic mouse model of HD. In addition, mutant huntingtin was found to disrupt transcription of TH and dopamine beta-hydroxylase (DbetaH) promoter reporter constructs. In situ hybridization revealed extensive loss of TH mRNA and decreased dopaminergic cell size in human HD substantia nigra. TH-immunoreactive protein was reduced in human grade 4 HD substantia nigra by 32% compared to age-matched controls. These findings implicate abnormalities in dopamine neurotransmission in HD and may provide new insights into targets for pharmacotherapy.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine beta-Hydroxylase,
http://linkedlifedata.com/resource/pubmed/chemical/HD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hdh protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hdh protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0169-328X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
119
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28-36
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:14597227-Aged,
pubmed-meshheading:14597227-Animals,
pubmed-meshheading:14597227-Disease Models, Animal,
pubmed-meshheading:14597227-Dopamine,
pubmed-meshheading:14597227-Dopamine beta-Hydroxylase,
pubmed-meshheading:14597227-Female,
pubmed-meshheading:14597227-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:14597227-Humans,
pubmed-meshheading:14597227-Huntington Disease,
pubmed-meshheading:14597227-Male,
pubmed-meshheading:14597227-Mice,
pubmed-meshheading:14597227-Mice, Transgenic,
pubmed-meshheading:14597227-Middle Aged,
pubmed-meshheading:14597227-Mutation,
pubmed-meshheading:14597227-Nerve Tissue Proteins,
pubmed-meshheading:14597227-Neurons,
pubmed-meshheading:14597227-Nuclear Proteins,
pubmed-meshheading:14597227-PC12 Cells,
pubmed-meshheading:14597227-Promoter Regions, Genetic,
pubmed-meshheading:14597227-RNA, Messenger,
pubmed-meshheading:14597227-Rats,
pubmed-meshheading:14597227-Substantia Nigra,
pubmed-meshheading:14597227-Transcription, Genetic,
pubmed-meshheading:14597227-Tyrosine 3-Monooxygenase
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pubmed:year |
2003
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pubmed:articleTitle |
Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology.
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pubmed:affiliation |
Department of Neurology, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, 114 16th Street, B114-2000, Charlestown, MA 02129-4404, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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