Source:http://linkedlifedata.com/resource/pubmed/id/18398426
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2008-5-26
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pubmed:abstractText |
Defects in cellular quality control mechanisms are thought to contribute to the neuropathology of Parkinson's disease (PD). Overexpressing heat shock proteins (HSPs) may constitute a powerful therapeutic strategy for PD, because they boost the ability of the cell to eliminate unwanted proteins. We investigated the neuroprotective potential of HSP70, HSP40, and H-BH, a constitutively active form of heat shock factor 1, in a rat model of PD based on adeno-associated virus (AAV) vector-mediated overexpression of CDCrel-1, a parkin substrate known to be toxic to dopaminergic neurons. AAV vector-mediated overexpression of H-BH and of HSP70 afforded similar levels of protection against CDCrel-1 toxicity, with approximately 20% improvement in survival of dopaminergic neurons as compared to the controls. The assessment of protection conferred was made using tyrosine hydroxylase (TH) and HuC/D immunohistochemistry and Fluoro-Gold retrograde tracing, and by observing the extent of preservation of spontaneous function and also the extent of drug-induced motor function. In contrast to H-BH and HSP70, HSP40 overexpression exacerbated CDCrel-1-mediated cell death. Real-time reverse transcriptase (RT)-PCR analysis showed that H-BH had the effect of upregulating endogenous HSP70 and HSP40 mRNA levels 10-fold and 4-fold over basal levels, respectively, whereas AAV vector-mediated HSP70 and HSP40 mRNA levels were over 100-fold higher. Our results suggest that a comparatively modest upregulation of multiple HSPs may be an effective approach for achieving significant neuroprotection in PD.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNAJB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HSP40 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SEPT5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sept5 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Septins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/heat shock transcription factor
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1525-0024
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1048-55
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:18398426-Animals,
pubmed-meshheading:18398426-Behavior, Animal,
pubmed-meshheading:18398426-Cell Cycle Proteins,
pubmed-meshheading:18398426-Cell Nucleus,
pubmed-meshheading:18398426-DNA-Binding Proteins,
pubmed-meshheading:18398426-Dependovirus,
pubmed-meshheading:18398426-Dopamine,
pubmed-meshheading:18398426-Gene Expression Regulation,
pubmed-meshheading:18398426-HSP40 Heat-Shock Proteins,
pubmed-meshheading:18398426-HSP70 Heat-Shock Proteins,
pubmed-meshheading:18398426-Humans,
pubmed-meshheading:18398426-Models, Biological,
pubmed-meshheading:18398426-Neurons,
pubmed-meshheading:18398426-Septins,
pubmed-meshheading:18398426-Transcription Factors
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pubmed:year |
2008
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pubmed:articleTitle |
HSP70 and constitutively active HSF1 mediate protection against CDCrel-1-mediated toxicity.
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pubmed:affiliation |
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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