Intranuclear Inclusions of Expanded Polyglutamine Protein in Spinocerebellar Ataxia Type 3
The mechanism of neurodegeneration in CAG/polyglutamine repeat expansion diseases is unknown but is thought to occur at the protein level. Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiq...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 1997-08, Vol.19 (2), p.333-344 |
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| container_title | Neuron (Cambridge, Mass.) |
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| creator | Paulson, H.L Perez, M.K Trottier, Y Trojanowski, J.Q Subramony, S.H Das, S.S Vig, P Mandel, J.-L Fischbeck, K.H Pittman, R.N |
| description | The mechanism of neurodegeneration in CAG/polyglutamine repeat expansion diseases is unknown but is thought to occur at the protein level. Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiquitinated intranuclear inclusions selectively in neurons of affected brain regions. We further provide evidence in vitro for a model of disease in which an expanded polyglutamine-containing fragment recruits full-length protein into insoluble aggregates. Together with recent findings from transgenic models, our results suggest that intranuclear aggregation of the expanded protein is a unifying feature of CAG/polyglutamine diseases and may be initiated or catalyzed by a glutamine-containing fragment of the disease protein. |
| doi_str_mv | 10.1016/S0896-6273(00)80943-5 |
| format | Article |
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Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiquitinated intranuclear inclusions selectively in neurons of affected brain regions. We further provide evidence in vitro for a model of disease in which an expanded polyglutamine-containing fragment recruits full-length protein into insoluble aggregates. 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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Glutamine - metabolism Humans Immunohistochemistry Life Sciences Machado-Joseph Disease - metabolism Models, Neurological Neurons and Cognition Proteins - metabolism |
| title | Intranuclear Inclusions of Expanded Polyglutamine Protein in Spinocerebellar Ataxia Type 3 |
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