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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2000-11-3
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pubmed:abstractText |
Among the eight progressive neurodegenerative diseases caused by polyglutamine expansions, spinocerebellar ataxia type 7 (SCA7) is the only one to display degeneration in both brain and retina. We show here that mice overexpressing full-length mutant ataxin-7[Q90] either in Purkinje cells or in rod photoreceptors have deficiencies in motor coordination and vision, respectively. In both models, although with different time courses, an N-terminal fragment of mutant ataxin-7 accumulates into ubiquitinated nuclear inclusions that recruit a distinct set of chaperone/proteasome subunits. A severe degeneration is caused by overexpression of ataxin-7[Q90] in rods, whereas a similar overexpression of normal ataxin-7[Q10] has no obvious effect. The degenerative process is not limited to photoreceptors, showing secondary alterations of post-synaptic neurons. These findings suggest that proteolytic cleavage of mutant ataxin-7 and trans-neuronal responses are implicated in the pathogenesis of SCA7.
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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 |
Oct
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pubmed:issn |
0964-6906
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2491-506
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11030754-Animals,
pubmed-meshheading:11030754-Cell Nucleus,
pubmed-meshheading:11030754-Cerebellum,
pubmed-meshheading:11030754-Electroretinography,
pubmed-meshheading:11030754-Humans,
pubmed-meshheading:11030754-Mice,
pubmed-meshheading:11030754-Mice, Transgenic,
pubmed-meshheading:11030754-Molecular Chaperones,
pubmed-meshheading:11030754-Nerve Degeneration,
pubmed-meshheading:11030754-Nerve Tissue Proteins,
pubmed-meshheading:11030754-Peptides,
pubmed-meshheading:11030754-Phenotype,
pubmed-meshheading:11030754-Protein Processing, Post-Translational,
pubmed-meshheading:11030754-Purkinje Cells,
pubmed-meshheading:11030754-Retina,
pubmed-meshheading:11030754-Retinal Degeneration,
pubmed-meshheading:11030754-Retinal Rod Photoreceptor Cells,
pubmed-meshheading:11030754-Spinocerebellar Ataxias,
pubmed-meshheading:11030754-Trinucleotide Repeats,
pubmed-meshheading:11030754-Ubiquitins
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pubmed:year |
2000
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pubmed:articleTitle |
Expanded polyglutamines induce neurodegeneration and trans-neuronal alterations in cerebellum and retina of SCA7 transgenic mice.
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pubmed:affiliation |
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch cedex, CU de Strasbourg, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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