Source:http://linkedlifedata.com/resource/pubmed/id/20537899
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2010-7-12
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| pubmed:abstractText |
Neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein are a hallmark of Alzheimer's disease (AD) and related tauopathies. Tau hyperphosphorylation is thought to promote aggregation with subsequent tangle formation. Reducing tau phosphorylation by boosting the activity of the key phosphatase/s that mediate dephosphorylation of tau could be a viable clinical strategy in AD. One of the key phosphatases implicated in regulating tau protein phosphorylation is the serine-threonine phosphatase PP2A. We have determined that sodium selenate can act as a specific agonist for PP2A, significantly boosting phosphatase activity. Acute treatment of either neuroblastoma cells or normal aged mice with sodium selenate rapidly reduced tau protein phosphorylation. Sodium selenate-treated transgenic TAU441 mice had significantly lower levels of phospho- and total tau levels in the hippocampus and amygdala compared with controls and exhibited significantly improved spatial learning and memory on the Morris Water Maze task. Sodium selenate is a specific activator of PP2A with excellent oral bioavailability, and favourable central nervous system penetrating properties. Clinical studies in patients with AD are envisaged in the near future.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
|
| pubmed:issn |
1532-2653
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2010 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1025-33
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| pubmed:meshHeading |
pubmed-meshheading:20537899-Alzheimer Disease,
pubmed-meshheading:20537899-Analysis of Variance,
pubmed-meshheading:20537899-Animals,
pubmed-meshheading:20537899-Blotting, Western,
pubmed-meshheading:20537899-Cell Line, Tumor,
pubmed-meshheading:20537899-Cells, Cultured,
pubmed-meshheading:20537899-Disease Models, Animal,
pubmed-meshheading:20537899-Hippocampus,
pubmed-meshheading:20537899-Humans,
pubmed-meshheading:20537899-Immunohistochemistry,
pubmed-meshheading:20537899-Immunoprecipitation,
pubmed-meshheading:20537899-Maze Learning,
pubmed-meshheading:20537899-Memory Disorders,
pubmed-meshheading:20537899-Mice,
pubmed-meshheading:20537899-Mice, Transgenic,
pubmed-meshheading:20537899-Organ Culture Techniques,
pubmed-meshheading:20537899-Phosphorylation,
pubmed-meshheading:20537899-Protein Phosphatase 2,
pubmed-meshheading:20537899-Rats,
pubmed-meshheading:20537899-Rats, Wistar,
pubmed-meshheading:20537899-Rotarod Performance Test,
pubmed-meshheading:20537899-Selenium Compounds,
pubmed-meshheading:20537899-tau Proteins
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| pubmed:year |
2010
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| pubmed:articleTitle |
Sodium selenate specifically activates PP2A phosphatase, dephosphorylates tau and reverses memory deficits in an Alzheimer's disease model.
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| pubmed:affiliation |
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville 3010, Victoria, Australia. niallmcorcoran@gmail.com
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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