Platelet protease nexin-2/amyloid beta-protein precursor. Possible pathologic and physiologic functions.
The amyloid beta-protein and its parent protein, amyloid beta-protein precursor (APP), are major constituents of neuritic plaques and cerebrovascular deposits in Alzheimer's disease and Down's syndrome. We reported that the protease inhibitor protease nexin-2 (PN-2) is the secreted form of APP that contains the Kunitz protease inhibitor domain. Previous studies suggested that circulating forms of PN-2/APP exist. Recently, we reported that PN-2/APP is a platelet alpha granule protein and is secreted upon platelet activation. Subsequent studies revealed that platelets are the major circulating repository for PN-2/APP and may contribute to its deposition in Alzheimer's disease. Protease inhibition measurements demonstrated that PN-2/APP is a potent inhibitor of certain serine proteases, particularly intrinsic blood coagulation factor XIa. Together, these findings indicate that PN-2/APP regulates blood coagulation, and possibly other proteolytic events, at sites of vascular injury.
Van Nostrand
W E
WE
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Schmaier
A H
AH
Farrow
J S
JS
Cunningham
D D
DD
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000097:blood / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D058255:Protease Nexins; D011956:Receptors, Cell Surface
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface