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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2006-9-4
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pubmed:abstractText |
Huntington's disease (HD) is a progressive neurodegenerative disorder for which only symptomatic treatments of limited effectiveness are available. Preventing early misfolding steps and thereby aggregation of the polyglutamine (polyQ)-containing protein huntingtin (htt) in neurons of patients may represent an attractive therapeutic strategy to postpone the onset and progression of HD. Here, we demonstrate that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) potently inhibits the aggregation of mutant htt exon 1 protein in a dose-dependent manner. Dot-blot assays and atomic force microscopy studies revealed that EGCG modulates misfolding and oligomerization of mutant htt exon 1 protein in vitro, indicating that it interferes with very early events in the aggregation process. Also, EGCG significantly reduced polyQ-mediated htt protein aggregation and cytotoxicity in an yeast model of HD. When EGCG was fed to transgenic HD flies overexpressing a pathogenic htt exon 1 protein, photoreceptor degeneration and motor function improved. These results indicate that modulators of htt exon 1 misfolding and oligomerization like EGCG are likely to reduce polyQ-mediated toxicity in vivo. Our studies may provide the basis for the development of a novel pharmacotherapy for HD and related polyQ disorders.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0964-6906
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pubmed:author |
pubmed-author:DuennwaldMartinM,
pubmed-author:EhrnhoeferDagmar EDE,
pubmed-author:EngemannSabineS,
pubmed-author:LegleiterJustinJ,
pubmed-author:LindquistSusanS,
pubmed-author:MarkovicPhoebeP,
pubmed-author:MarshJ LawrenceJL,
pubmed-author:MuchowskiPaul JPJ,
pubmed-author:RoarkMargaretM,
pubmed-author:ThompsonLeslie MLM,
pubmed-author:WackerJennifer LJL,
pubmed-author:WankerErich EEE
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2743-51
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16893904-Animals,
pubmed-meshheading:16893904-Animals, Genetically Modified,
pubmed-meshheading:16893904-Camellia sinensis,
pubmed-meshheading:16893904-Catechin,
pubmed-meshheading:16893904-Drosophila melanogaster,
pubmed-meshheading:16893904-Exons,
pubmed-meshheading:16893904-Humans,
pubmed-meshheading:16893904-Huntington Disease,
pubmed-meshheading:16893904-Microscopy, Atomic Force,
pubmed-meshheading:16893904-Models, Biological,
pubmed-meshheading:16893904-Motor Neurons,
pubmed-meshheading:16893904-Multiprotein Complexes,
pubmed-meshheading:16893904-Mutation,
pubmed-meshheading:16893904-Nerve Degeneration,
pubmed-meshheading:16893904-Nerve Tissue Proteins,
pubmed-meshheading:16893904-Nuclear Proteins,
pubmed-meshheading:16893904-Photoreceptor Cells, Invertebrate,
pubmed-meshheading:16893904-Phytotherapy,
pubmed-meshheading:16893904-Protein Conformation,
pubmed-meshheading:16893904-Protein Folding,
pubmed-meshheading:16893904-Protein Structure, Quaternary,
pubmed-meshheading:16893904-Recombinant Fusion Proteins,
pubmed-meshheading:16893904-Saccharomyces cerevisiae
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pubmed:year |
2006
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pubmed:articleTitle |
Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models.
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pubmed:affiliation |
Max Delbrueck Center for Molecular Medicine, Department of Neuroproteomics, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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