Linked Life Data

20705605

Source:http://linkedlifedata.com/resource/pubmed/id/20705605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2010-10-18
pubmed:abstractText
Several missense mutations in the protein kinase C? (?PKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant ?PKC found in SCA14 is susceptible to aggregation, which induces apoptotic cell death. The disaccharide trehalose has been reported to inhibit aggregate formation and to alleviate symptoms in cellular and animal models of Huntington disease, Alzheimer disease, and prion disease. Here, we show that trehalose can be incorporated into SH-SY5Y cells and reduces the aggregation of mutant ?PKC-GFP, thereby inhibiting apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells (PCs). Trehalose acts by directly stabilizing the conformation of mutant ?PKC without affecting protein turnover. Trehalose was also found to alleviate the improper development of dendrites in PCs expressing mutant ?PKC-GFP without aggregates but not in PCs with aggregates. In PCs without aggregates, trehalose improves the mobility and translocation of mutant ?PKC-GFP, probably by inhibiting oligomerization and thereby alleviating the improper development of dendrites. These results suggest that trehalose counteracts various cellular dysfunctions that are triggered by mutant ?PKC in both neuronal cell lines and primary cultured PCs by inhibiting oligomerization and aggregation of mutant ?PKC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33252-64
pubmed:dateRevised
2011-10-24
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Effect of trehalose on the properties of mutant {gamma}PKC, which causes spinocerebellar ataxia type 14, in neuronal cell lines and cultured Purkinje cells.
pubmed:affiliation
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't