Source:http://linkedlifedata.com/resource/pubmed/id/18210139
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2008-2-19
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| pubmed:abstractText |
Phosphorylated Smad2/3 (pSmad2/3), the central mediators of transforming growth factor (TGF)-beta signaling, were recently identified in tau-positive inclusions in certain neurodegenerative disorders. To clarify whether the localization of pSmad2/3 is altered in amyotrophic lateral sclerosis (ALS), we immunohistochemically examined spinal cords from sporadic ALS (SALS), from familial ALS (FALS) patients with the A4V mutation in their Cu/Zn superoxide dismutase (SOD1) gene, and from G93A mutant SOD1 transgenic (mSOD1 Tg) mice. In control spinal cords, pSmad2/3 immunoreactivity was observed exclusively in neuronal and glial nuclei. In SALS and FALS patients the nuclei showed increased immunoreactivity for pSmad2/3. Noticeably, round hyaline inclusions (RHIs) and skein-like inclusions of SALS patients were immunoreactive for pSmad2/3. Double immunofluorescence staining for pSmad2/3 and transactive response-DNA-binding protein (TDP)-43 revealed co-localization of these proteins within RHIs. In contrast, Bunina bodies in SALS and Lewy body-like hyaline inclusions (LBHIs) in FALS were devoid of labeling for pSmad2/3. Similarly, in the mSOD1 Tg mice pSmad2/3 immunoreactivity was increased in the nuclei, while LBHIs were not labeled. These findings suggest increased TGF-beta-Smad signaling in SALS, FALS, and mSOD1 Tg mice, as well as impaired TGF-beta signal transduction in RHI-bearing neurons of SALS patients, presumably at the step of pSmad2/3 translocation into the nucleus. The pathomechanisms, including the process of inclusion development, appears to be different between SALS and mSOD1-related FALS or Tg mice.
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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 |
Mar
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| pubmed:issn |
0001-6322
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
115
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
327-34
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| pubmed:meshHeading |
pubmed-meshheading:18210139-Adult,
pubmed-meshheading:18210139-Aged,
pubmed-meshheading:18210139-Aged, 80 and over,
pubmed-meshheading:18210139-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:18210139-Animals,
pubmed-meshheading:18210139-Cell Nucleus,
pubmed-meshheading:18210139-Disease Models, Animal,
pubmed-meshheading:18210139-Female,
pubmed-meshheading:18210139-Fluorescent Antibody Technique,
pubmed-meshheading:18210139-Humans,
pubmed-meshheading:18210139-Immunohistochemistry,
pubmed-meshheading:18210139-Inclusion Bodies,
pubmed-meshheading:18210139-Male,
pubmed-meshheading:18210139-Mice,
pubmed-meshheading:18210139-Mice, Transgenic,
pubmed-meshheading:18210139-Middle Aged,
pubmed-meshheading:18210139-Phosphorylation,
pubmed-meshheading:18210139-Protein Transport,
pubmed-meshheading:18210139-Smad2 Protein,
pubmed-meshheading:18210139-Smad3 Protein,
pubmed-meshheading:18210139-Spinal Cord
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| pubmed:year |
2008
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| pubmed:articleTitle |
Phosphorylated Smad2/3 immunoreactivity in sporadic and familial amyotrophic lateral sclerosis and its mouse model.
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| pubmed:affiliation |
Department of Neurology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, Osaka 570-8507, Japan.
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| pubmed:publicationType |
Journal Article
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