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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-7-1
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pubmed:abstractText |
Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease. Here we identify a new mechanism of inclusion formation by showing that decreased dynein function impairs autophagic clearance of aggregate-prone proteins. We show that mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models. Furthermore, loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II in both cell culture and mouse models, compatible with impaired autophagosome-lysosome fusion.
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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/9-(2-hydroxy-3-nonyl)adenine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylyl Imidodiphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Dyneins,
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/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Synucleins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1061-4036
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
771-6
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15980862-Adenine,
pubmed-meshheading:15980862-Adenylyl Imidodiphosphate,
pubmed-meshheading:15980862-Animals,
pubmed-meshheading:15980862-Autophagy,
pubmed-meshheading:15980862-Behavior, Animal,
pubmed-meshheading:15980862-Brain,
pubmed-meshheading:15980862-COS Cells,
pubmed-meshheading:15980862-Cercopithecus aethiops,
pubmed-meshheading:15980862-Crosses, Genetic,
pubmed-meshheading:15980862-Diptera,
pubmed-meshheading:15980862-Dyneins,
pubmed-meshheading:15980862-Humans,
pubmed-meshheading:15980862-Huntington Disease,
pubmed-meshheading:15980862-Inclusion Bodies,
pubmed-meshheading:15980862-Mice,
pubmed-meshheading:15980862-Mice, Mutant Strains,
pubmed-meshheading:15980862-Mutation,
pubmed-meshheading:15980862-Nerve Tissue Proteins,
pubmed-meshheading:15980862-Nuclear Proteins,
pubmed-meshheading:15980862-PC12 Cells,
pubmed-meshheading:15980862-Proteasome Endopeptidase Complex,
pubmed-meshheading:15980862-Rats,
pubmed-meshheading:15980862-Synucleins
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pubmed:year |
2005
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pubmed:articleTitle |
Dynein mutations impair autophagic clearance of aggregate-prone proteins.
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pubmed:affiliation |
Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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