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| Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3 |
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| Author(s): Paulson HL, Perez MK, Trottier Y, Trojanowski JQ, Subramony SH, Das SS, Vig P, Mandel JL, Fischbeck KH, Pittman RN |
| Source: NEURON Volume: 19 Issue: 2 Pages: 333-344 Published: AUG 1997 |
| Times Cited: 466 References: 66 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV PENN, SCH MED, DEPT PHARMACOL, PHILADELPHIA, PA 19104 USA
2. UNIV PENN, SCH MED, DEPT NEUROL, PHILADELPHIA, PA 19104 USA
3. UNIV PENN, SCH MED, DEPT PATHOL, PHILADELPHIA, PA 19104 USA
4. INST GENET & BIOL MOL & CELLULAIRE, F-67404 ILLKIRCH GRAFFENSTADEN, FRANCE
5. UNIV MISSISSIPPI, DEPT NEUROL, JACKSON, MS 38677 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Neurosciences |
| IDS Number: XU146 |
| ISSN: 0896-6273 |
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