Linked Life Data

9428662

Source:http://linkedlifedata.com/resource/pubmed/id/9428662

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-30
pubmed:abstractText
Amyloid beta-protein is a 4-kDa peptide which originates from proteolysis of a larger protein precursor (APP) and accumulates in senile plaques in brains of Alzheimer's disease (AD) patients. Since secreted APP inhibits factors IXa, Xa and XIa, and thrombin appears to play a role in APP secretion and proteolysis, a relationship between hemostasis system and APP metabolism seems to exist. In this work we investigate the susceptibility to proteolytic cleavage by factor Xa of a fusion construct containing full-length APP prepared in bacteria, and demonstrate that both APP695 and APP770 are substrates for this protease. Factor Xa was found to cleave APP after arginines 102, 268, 510, 573 and 601 (APP695 numeration); most of these sites appear to be common for different coagulation factors. In addition, APP incubation with factor Xa generates an array of six potentially amyloidogenic fragments. Comparative kinetic analysis of APP695 and APP770 cleavage by factor Xa suggests that Kunitz-type inhibitor-containing isoforms exert an inhibitory effect on the protease. However, this inhibition is far from complete even at a 5-fold molar excess of inhibitor. Our results raise the possibility that proteases from the coagulation cascade may contribute to APP proteolysis, and support the notion that these proteases play a role in AD pathogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
1343
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Proteolysis of Alzheimer's disease beta-amyloid precursor protein by factor Xa.
pubmed:affiliation
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't