Linked Life Data

18374587

Source:http://linkedlifedata.com/resource/pubmed/id/18374587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-4-28
pubmed:abstractText
Alzheimer's disease and prion diseases (e.g., Creutzfeldt-Jakob disease) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. However, the intracellular events in prion diseases and their relation with the processing of the amyloid precursor protein (APP) and beta-amyloid generation are unknown. The adaptor protein Dab1 may regulate intracellular trafficking and secretase-mediated proteolysis in APP processing. However, a putative relationship between prion diseases and Dab1/APP interactions is lacking. Thus, we examined, in inoculated animals, whether Dab1 and APP processing are targets of the intracellular events triggered by extracellular exposure to PrP(106-126) peptide. Our in vitro results indicate that PrP(106-126) peptide induces tyrosine phosphorylation of Dab1 by activated members of the Src family of tyrosine kinases (SFK), which implies further Dab1 degradation. We also corroborate these results in Dab1 protein levels in prion-inoculated hamsters. Finally, we show that fibrillar prion peptides have a dual effect on APP processing and beta-amyloid production. First, they block APP trafficking at the cell membrane, thus decreasing beta-amyloid production. In parallel, they reduce Dab1 levels, which also alter APP processing. Lastly, neuronal cultures from Dab1-deficient mice showed severe impairment of APP processing with reduced sAPP secretion and A beta production after prion peptide incubation. Taken together, these data indicate a link between intracellular events induced by exposure to extracellular fibrillar peptide or PrP(res), and APP processing and implicate Dab1 in this link.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1095-953X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
243-54
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18374587-Amyloid beta-Peptides, pubmed-meshheading:18374587-Amyloid beta-Protein Precursor, pubmed-meshheading:18374587-Animals, pubmed-meshheading:18374587-Cells, Cultured, pubmed-meshheading:18374587-Cerebral Cortex, pubmed-meshheading:18374587-Cricetinae, pubmed-meshheading:18374587-Female, pubmed-meshheading:18374587-Humans, pubmed-meshheading:18374587-Mesocricetus, pubmed-meshheading:18374587-Mice, pubmed-meshheading:18374587-Mice, Inbred BALB C, pubmed-meshheading:18374587-Mice, Inbred C57BL, pubmed-meshheading:18374587-Mice, Knockout, pubmed-meshheading:18374587-Mice, Mutant Strains, pubmed-meshheading:18374587-Nerve Tissue Proteins, pubmed-meshheading:18374587-Neurons, pubmed-meshheading:18374587-Peptide Fragments, pubmed-meshheading:18374587-Phosphorylation, pubmed-meshheading:18374587-PrP 27-30 Protein, pubmed-meshheading:18374587-Pregnancy, pubmed-meshheading:18374587-Prions, pubmed-meshheading:18374587-Protein Processing, Post-Translational
pubmed:year
2008
pubmed:articleTitle
Fibrillar prion peptide PrP(106-126) treatment induces Dab1 phosphorylation and impairs APP processing and Abeta production in cortical neurons.
pubmed:affiliation
Cellular and Molecular Basis of Neurodegeneration and Neurorepair, Department of Cell Biology, University of Barcelona, Spain.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't