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

William E. Van Nostrand, Steven L. Wagner, Michiyasu Suzuki, Ben H. Choi, Jeffrey S. Farrow, James W. Geddes, Carl W. Cotman, Dennis D. Cunningham

Research output: Contribution to journalArticlepeer-review

350 Scopus citations

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 trypsin. 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). Amyloid β-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome. A monoclonal antibody against PN-II (designated mAbP2-1) 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 × 10-10 M. 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 disease.

Original languageEnglish
Pages (from-to)546-549
Number of pages4
JournalNature
Volume341
Issue number6242
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General

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