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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-2-4
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pubmed:abstractText |
Inhibition of polyglutamine-induced protein aggregation could provide treatment options for polyglutamine diseases such as Huntington disease. Here we showed through in vitro screening studies that various disaccharides can inhibit polyglutamine-mediated protein aggregation. We also found that various disaccharides reduced polyglutamine aggregates and increased survival in a cellular model of Huntington disease. Oral administration of trehalose, the most effective of these disaccharides, decreased polyglutamine aggregates in cerebrum and liver, improved motor dysfunction and extended lifespan in a transgenic mouse model of Huntington disease. We suggest that these beneficial effects are the result of trehalose binding to expanded polyglutamines and stabilizing the partially unfolded polyglutamine-containing protein. Lack of toxicity and high solubility, coupled with efficacy upon oral administration, make trehalose promising as a therapeutic drug or lead compound for the treatment of polyglutamine diseases. The saccharide-polyglutamine interaction identified here thus provides a new therapeutic strategy for polyglutamine diseases.
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pubmed:commentsCorrections |
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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/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/HD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hdh protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myoglobin,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Trehalose,
http://linkedlifedata.com/resource/pubmed/chemical/polyglutamine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1078-8956
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
148-54
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14730359-Animals,
pubmed-meshheading:14730359-Brain,
pubmed-meshheading:14730359-Cell Death,
pubmed-meshheading:14730359-Cell Line,
pubmed-meshheading:14730359-Disease Models, Animal,
pubmed-meshheading:14730359-Glucose,
pubmed-meshheading:14730359-Humans,
pubmed-meshheading:14730359-Huntington Disease,
pubmed-meshheading:14730359-Liver,
pubmed-meshheading:14730359-Mice,
pubmed-meshheading:14730359-Mice, Transgenic,
pubmed-meshheading:14730359-Motor Activity,
pubmed-meshheading:14730359-Myoglobin,
pubmed-meshheading:14730359-Nerve Tissue Proteins,
pubmed-meshheading:14730359-Neurons,
pubmed-meshheading:14730359-Nuclear Proteins,
pubmed-meshheading:14730359-Peptides,
pubmed-meshheading:14730359-Trehalose
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pubmed:year |
2004
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pubmed:articleTitle |
Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease.
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pubmed:affiliation |
Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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