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Protease nexin-II, a potent anti-chymotrypsin, shows identity to amyloid β-protein precursor

Nature volume 341, pages 546–549 (1989)Cite this article

Abstract

PROTEASE nexin-II (PN-II) is a protease inhibitor that forms SDS-resistant inhibitory complexes with the epidermal growth factor (EGF)-binding protein, the γ-subunit of nerve growth factor, and trypsin1–3. The properties of PN-II indicate that it has a role in the regulation of certain proteases in the extracellular environment. Here we describe more of the amino-acid sequence of PN-II and its identity to the deduced sequence of the amyloid β-protein precursor (APP)4,5. Amyloid β-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome6–9. A monoclonal antibody against PN-II (designated mAbP2-l) recognized PN-II in immunoblots of serum-free culture medium from human glioblastoma cells and neuroblastoma cells, as well as in homogenates of normal and Alzheimer's disease brains. In addition, mAbP2-1 stained neuritic plaques in Alzheimer's disease brain. PN-II was a potent inhibitor of chymotrypsin with an inhibition constant Ki of 6 × 10−10M. Together, these data demonstrate that PN-II and APP are probably the same protein. The regulation of extracellular proteolysis by PN-II and the deposition of at least parts of the molecule in senile plaques is consistent with previous reports that implicate altered proteolysis in the pathogenesis of Alzheimer's disease4,5,10–12.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of California, Irvine, California, 92717, USA

    William E. Van Nostrand, Steven L. Wagner, Jeffrey S. Farrow & Dennis D. Cunningham

  2. Department of Pathology, University of California, Irvine, California, 92717, USA

    Michiyasu Suzuki & Ben H. Choi

  3. Department of Psychobiology, University of California, Irvine, California, 92717, USA

    James W. Geddes & Carl W. Cotman

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  1. William E. Van Nostrand
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  2. Steven L. Wagner
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  4. Ben H. Choi
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  6. James W. Geddes
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  7. Carl W. Cotman
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  8. Dennis D. Cunningham
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Nostrand, W., Wagner, S., Suzuki, M. et al. Protease nexin-II, a potent anti-chymotrypsin, shows identity to amyloid β-protein precursor. Nature 341, 546–549 (1989). https://doi.org/10.1038/341546a0

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