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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2009-7-6
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pubmed:abstractText |
Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion of polyglutamines which makes huntingtin more resistant to degradation. Parkin is an ubiquitin ligase which promotes proteosomal degradation of abnormal proteins. We investigated whether partial suppression of parkin increases HD phenotype. We studied the behavior and brain histology and biochemistry of the mice produced by interbreeding of R6/1 (model of HD in mice) with Park-2(-/-) (parkin null mice): R6/1, WT (wild-type), PK(+/-) (hemizygotic deletion of Park-2) and R6/1/PK(+/-). R6/1 and R6/1/PK(+/-) mice had abnormal motor and exploratory behavior. R6/1/PK(+/-) mice were more akinetic. These two groups of mice had severe but similar loss of nigrostriatal dopamine neurons and monoamine levels in striatum. R6/1/PK(+/-) mice had fewer huntingtin inclusions and a greater number of TUNEL(+) cells than R6/1 in striatum but there were no differences in the hippocampus. DARPP-32 protein was equally reduced in striatum of R6/1 and R6/1/PK(+/-) mice. Striatal levels of GSH were increased, of HSP-70 reduced and of CHIP unchanged in both R6/1 and R6/1/PK(+/-) mice. LC-3 II/I ratios were significantly increased in striatum of R6/1/PK(+/-) mice. Partial suppression of parkin slightly aggravates the phenotype in R6/1 mice, confirming a pathogenic role of the UPS in the processing of mutant huntingtin. The absence of massive additional cellular lesions in R6/1/PK(+/-) mice suggests the existence of compensatory mechanisms, such as autophagy, for the processing of huntingtin.
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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/Biogenic Monoamines,
http://linkedlifedata.com/resource/pubmed/chemical/CHIP protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/HD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP1LC3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/parkin protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1872-6240
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pubmed:author |
pubmed-author:CasarejosMaría JoséMJ,
pubmed-author:GómezAnaA,
pubmed-author:LucasJosé JJJ,
pubmed-author:MenaMaría AngelesMA,
pubmed-author:PeruchoJuanJ,
pubmed-author:RodalIzaskunI,
pubmed-author:Rodríguez-NavarroJosé AntonioJA,
pubmed-author:RuízCarolinaC,
pubmed-author:RubioIsabelI,
pubmed-author:Tomás-ZapicoCristinaC,
pubmed-author:de YébenesJusto GarcíaJG
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
1281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
91-100
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pubmed:meshHeading |
pubmed-meshheading:19464273-Animals,
pubmed-meshheading:19464273-Biogenic Monoamines,
pubmed-meshheading:19464273-Brain,
pubmed-meshheading:19464273-Cell Death,
pubmed-meshheading:19464273-Disease Models, Animal,
pubmed-meshheading:19464273-Dopamine,
pubmed-meshheading:19464273-Exploratory Behavior,
pubmed-meshheading:19464273-HSP70 Heat-Shock Proteins,
pubmed-meshheading:19464273-Humans,
pubmed-meshheading:19464273-Huntington Disease,
pubmed-meshheading:19464273-Male,
pubmed-meshheading:19464273-Mice,
pubmed-meshheading:19464273-Mice, Knockout,
pubmed-meshheading:19464273-Mice, Mutant Strains,
pubmed-meshheading:19464273-Microtubule-Associated Proteins,
pubmed-meshheading:19464273-Motor Activity,
pubmed-meshheading:19464273-Nerve Tissue Proteins,
pubmed-meshheading:19464273-Neurons,
pubmed-meshheading:19464273-Nuclear Proteins,
pubmed-meshheading:19464273-Phenotype,
pubmed-meshheading:19464273-Ubiquitin-Protein Ligases
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pubmed:year |
2009
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pubmed:articleTitle |
Effects of partial suppression of parkin on huntingtin mutant R6/1 mice.
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pubmed:affiliation |
Servicio de Neurología, Hospital Ramón y Cajal, Madrid, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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