Linked Life Data

21355046

Source:http://linkedlifedata.com/resource/pubmed/id/21355046

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-4-22
pubmed:abstractText
Lesions containing abnormal aggregated tau protein are one of the diagnostic hallmarks of Alzheimer's disease (AD) and related tauopathy disorders. How aggregated tau leads to dementia remains enigmatic, although neuronal dysfunction and loss clearly contribute. We previously identified sut-2 as a gene required for tau neurotoxicity in a transgenic Caenorhabditis elegans model of tauopathy. Here, we further explore the role of sut-2 and show that overexpression of SUT-2 protein enhances tau-induced neuronal dysfunction, neurotoxicity and accumulation of insoluble tau. We also explore the relationship between sut-2 and its human homolog, mammalian SUT-2 (MSUT2) and find both proteins to be predominantly nuclear and localized to SC35-positive nuclear speckles. Using a cell culture model for the accumulation of pathological tau, we find that high tau levels lead to increased expression of MSUT2 protein. We analyzed MSUT2 protein in age-matched post-mortem brain samples from AD patients and observe a marked decrease in overall MSUT2 levels in the temporal lobe of AD patients. Analysis of post-mortem tissue from AD cases shows a clear reduction in neuronal MSUT2 levels in brain regions affected by tau pathology, but little change in regions lacking tau pathology. RNAi knockdown of MSUT2 in cultured human cells overexpressing tau causes a marked decrease in tau aggregation. Both cell culture and post-mortem tissue studies suggest that MSUT2 levels may influence neuronal vulnerability to tau toxicity and aggregation. Thus, neuroprotective strategies targeting MSUT2 may be of therapeutic interest for tauopathy disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1989-99
pubmed:meshHeading
pubmed-meshheading:21355046-Alzheimer Disease, pubmed-meshheading:21355046-Animals, pubmed-meshheading:21355046-Brain, pubmed-meshheading:21355046-Caenorhabditis elegans, pubmed-meshheading:21355046-Caenorhabditis elegans Proteins, pubmed-meshheading:21355046-Carrier Proteins, pubmed-meshheading:21355046-Cell Nucleus, pubmed-meshheading:21355046-Gene Knockdown Techniques, pubmed-meshheading:21355046-Genetic Predisposition to Disease, pubmed-meshheading:21355046-HEK293 Cells, pubmed-meshheading:21355046-Humans, pubmed-meshheading:21355046-Mice, pubmed-meshheading:21355046-Neurons, pubmed-meshheading:21355046-Protein Transport, pubmed-meshheading:21355046-RNA, Small Interfering, pubmed-meshheading:21355046-Solubility, pubmed-meshheading:21355046-Tauopathies, pubmed-meshheading:21355046-tau Proteins
pubmed:year
2011
pubmed:articleTitle
MSUT2 is a determinant of susceptibility to tau neurotoxicity.
pubmed:affiliation
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98108, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural