Evidence against a role for the Kunitz domain in amyloidogenic and secretory processing of the amyloid precursor protein

Uri S. Ladror, Russell E. Kohnken, Gary T. Wang, Arlene M. Manelli, Donald E. Frail, William L. Klein, Thomas F. Holzman*, Grant A. Krafft

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The effect of the Kunitz proteinase inhibitor (KPI) on potential β- amyloid precursor protein (βPP)-processing activities from control and Alzheimer's disease (AD) brains was examined using fluorogenic substrates designed to mimic the secretory and amyloidogenic cleavages in βPP. In addition, the level of secretion of KPI-containing βPP751 and KPI-lacking βPP695 from transfected cells was examined to assess the effect of the KPI on βPP secretion. βPP751 and βPP695, obtained from conditioned media of transfected cells, had no effect on proteinase activities against the secretory and amyloidogenic substrates in extracts from control and AD brains. At similar concentrations βPP751, but not βPP695, completely inhibited the activity of trypsin against these substrates. Serine proteinase inhibitors had only modest effects on activities from brain, whereas cysteine modification completely inhibited them, indicating that these proteinase activities were not of the serine type. Thus, the results do not support a role for the KPI in the secretion of βPP or in the amyloidogenic cleavage of βPP. The amounts of βPP695 and βPP751 collected from the media of transfected cells after 48 h of growth were similar, indicating an equal rate of secretion. This result suggests that the KPI domain in βPP751 did not inhibit the secretory cleavage in transfected cells.

Original languageEnglish (US)
Pages (from-to)2225-2230
Number of pages6
JournalJournal of neurochemistry
Issue number6
StatePublished - Dec 1994


  • Alzheimer's disease
  • Kunitz proteinase inhibitor
  • β-Amyloid precursor protein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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