Linked Life Data

20635090

Source:http://linkedlifedata.com/resource/pubmed/id/20635090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-8-18
pubmed:abstractText
Protein aggregation is a major pathological hallmark of many neurodegenerative disorders including polyglutamine diseases. Aggregation of the mutated form of the disease protein ataxin-3 into neuronal nuclear inclusions is well described in the polyglutamine disorder spinocerebellar ataxia type 3 (SCA3 or Machado-Joseph disease), although these inclusions are not thought to be directly pathogenic. Neuropil aggregates have not yet been described in SCA3. We performed a systematic immunohistochemical study of serial thick sections through brains of seven clinically diagnosed and genetically confirmed SCA3 patients. Using antibodies against ataxin-3, p62, ubiquitin, the polyglutamine marker 1C2 as well as TDP-43, we analyzed neuronal localization, composition and distribution of aggregates within SCA3 brains. The analysis revealed widespread axonal aggregates in fiber tracts known to undergo neurodegeneration in SCA3. Similar to neuronal nuclear inclusions, the axonal aggregates were ubiquitinated and immunopositive for the proteasome and autophagy associated shuttle protein p62, indicating involvement of neuronal protein quality control mechanisms. Rare TDP-43 positive axonal inclusions were also observed. Based on the correlation between affected fiber tracts and degenerating neuronal nuclei, we hypothesize that these novel axonal inclusions may be detrimental to axonal transport mechanisms and thereby contribute to degeneration of nerve cells in SCA3.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1432-0533
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
449-60
pubmed:dateRevised
2011-6-1
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Axonal inclusions in spinocerebellar ataxia type 3.
pubmed:affiliation
Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, 9713 RB Groningen, The Netherlands. Kay_Seidel@gmx.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural