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.
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 .
Which is the protein implicated in Spinocerebellar ataxia type 3?
Which is the protein implicated in Spinocerebellar ataxia type 3 ?
Ataxin-3
Ataxin-3