Linked Life Data

16409551

Source:http://linkedlifedata.com/resource/pubmed/id/16409551

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-13
pubmed:abstractText
Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease resulting from loss of Purkinje neurones within the cerebellum. The ubiquitin proteasome pathway (UPP) has been implicated in SCA1 but the role of proteolysis in the disease is still poorly understood. To further investigate this issue in vivo, genetic crosses were performed between an established mouse model of SCA1 and novel strains expressing elevated levels of wild type or mutant isoforms of ubiquitin. The K48R mutant isoform of ubiquitin (a dominant negative inhibitor of proteolysis) was found to significantly delay the deterioration of Purkinje neurones as evidenced by behavioural, morphological, and molecular indicators. This delay was accompanied by stabilization of p300/CBP, transcriptional mediators whose abundance and activity would otherwise decline in the course of the SCA1 disease, and persistence of protein kinase C gamma (PKCgamma), a protein involved in Purkinje cell dendritic development that is mutated in one form of spinocerebellar ataxia. Whereas the stabilization of p300/CBP was found to occur at the post-translational level the modulation of PKCgamma was at the level of transcription. These results are consistent with transcriptional dysregulation as a key mechanism in neurodegeneration through loss of p300/CBP. Further, the results suggest that the UPP is a potentially useful target for the development of novel therapies for the treatment of neurodegenerative disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0305-1846
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26-39
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Delayed spinocerebellar ataxia in transgenic mice expressing mutant ubiquitin.
pubmed:affiliation
Ottawa Health Research Institute, Ottawa, Ontario, Canada K1H 8L6.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't