Linked Life Data

21441896

Source:http://linkedlifedata.com/resource/pubmed/id/21441896

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-5-19
pubmed:abstractText
Formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as Alzheimer's disease or prion diseases. Moreover, increasing evidence indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease-associated proteins may share common structural features. Previous studies revealed that toxic effects of the scrapie prion protein (PrP(Sc)), a ?-sheet-rich isoform of the cellular PrP (PrP(C)), are dependent on neuronal expression of PrP(C). In this study, we demonstrate that PrP(C) has a more general effect in mediating neurotoxic signalling by sensitizing cells to toxic effects of various ?-sheet-rich (?) conformers of completely different origins, formed by (i) heterologous PrP, (ii) amyloid ?-peptide, (iii) yeast prion proteins or (iv) designed ?-peptides. Toxic signalling via PrP(C) requires the intrinsically disordered N-terminal domain (N-PrP) and the GPI anchor of PrP. We found that the N-terminal domain is important for mediating the interaction of PrP(C) with ?-conformers. Interestingly, a secreted version of N-PrP associated with ?-conformers and antagonized their toxic signalling via PrP(C). Moreover, PrP(C)-mediated toxic signalling could be blocked by an NMDA receptor antagonist or an oligomer-specific antibody. Our study indicates that PrP(C) can mediate toxic signalling of various ?-sheet-rich conformers independent of infectious prion propagation, suggesting a pathophysiological role of the prion protein beyond of prion diseases.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1460-2075
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2057-70
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The cellular prion protein mediates neurotoxic signalling of ?-sheet-rich conformers independent of prion replication.
pubmed:affiliation
Department of Metabolic Biochemistry, Neurobiochemistry, Adolf-Butenandt-Institute, Ludwig-Maximilians-University Munich, Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural