Linked Life Data

18284615

Source:http://linkedlifedata.com/resource/pubmed/id/18284615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-7-23
pubmed:abstractText
The microtubule-associated protein tau is abnormally hyperphosphorylated in the brains of individuals with Alzheimer disease and other tauopathies, and is believed to play a critical role in the pathogenesis of these diseases. While the mechanisms leading to abnormal tau phosphorylation remain elusive, the recent demonstration of reversible tau phosphorylation during hibernation provides an ideal physiological model to study this critical process in vivo. In this study, Arctic ground squirrels (AGS) during hibernation were used to study mechanisms related to tau hyperphosphorylation. Our data demonstrate that tau is hyperphosphorylated at all six sites (S199, T205, S214, S262, S396, and S404) examined in hibernating AGS. Interestingly, only three of these sites (S199, S262, and S404) are dephosphorylated in aroused animals, suggesting a reversible phosphorylation at selective sites. Summer-active AGS demonstrated the lowest tau phosphorylation at all these sites. To explore the mechanisms underlying increased tau phosphorylation during hibernation, the expression level and enzyme activity of various potential tau kinases and protein phosphatases were examined. The kinetic analysis of enzyme activity at different temperatures revealed differential changes in enzyme activity with temperature decline. Specifically, increased protein kinase A activity, decreased protein phosphatase 2A activity, as well as substantial contribution from glycogen synthase kinase-3beta, likely play a key role in increased tau phosphorylation during hibernation in AGS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2098-108
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Physiological regulation of tau phosphorylation during hibernation.
pubmed:affiliation
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural