Linked Life Data

20410122

Source:http://linkedlifedata.com/resource/pubmed/id/20410122

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2010-4-22
pubmed:abstractText
Spinal and bulbar muscular atrophy (SBMA) is a late-onset lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat, which encodes a polyglutamine tract in androgen receptor (AR). Although it is commonly held that the pathogenic polyglutamine proteins accumulate in neurons and thereby induce transcriptional dysregulation, the downstream molecular events have remained elusive. Here, we examined whether TGF-beta signaling is dysregulated in SBMA. Nuclear translocation of phosphorylated Smad2/3, a key step in TGF-beta signaling, is suppressed in the spinal motor neurons of male transgenic mice carrying the mutant human AR. A similar finding was also observed in the motor neurons, but not in Purkinje cells, of SBMA patients. The pathogenic AR, the causative protein of SBMA, inhibits the transcription of TGF-beta receptor type II (TbetaRII) via abnormal interactions with NF-Y and p300/CBP-associated factor. Furthermore, overexpression of TbetaRII dampens polyglutamine-induced cytotoxicity in a neuroblastoma cell line expressing the pathogenic AR. The present study thus indicates that disruption of TGF-beta due to the transcriptional dysregulation of TbetaRII is associated with polyglutamine-induced motor neuron damage in SBMA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5702-12
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Disrupted transforming growth factor-beta signaling in spinal and bulbar muscular atrophy.
pubmed:affiliation
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. ka2no@med.nagoya-u.ac.jp
pubmed:publicationType
Journal Article, Comparative Study