Protease nexin-1, an antithrombin with neurite outgrowth activity, is reduced in Alzheimer disease

S. L. Wagner, J. W. Geddes, C. W. Cotman, A. L. Lau, D. Gurwitz, P. J. Isackson, D. D. Cunningham

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137 Scopus citations


Protease nexin-1 (PN-1) is a cell-secreted protein that inhibits certain proteases, particularly thrombin, by forming SDS-stable complexes with the catalytic site serine of the protease. PN-1 was recently shown to be identical to a glial-derived neurite-promoting factor/glial-derived nexin present in rat brain. Its neurite outgrowth activity depends on inhibition of thrombin, presumably because thrombin brings about neurite retraction. Here we show that human brain contains PN-1 and that PN-1 activity in brains of individuals with Alzheimer disease (AD) was only 14% of control values (total of 14 AD patients and 7 control individuals). PN-1 activity in the hippocampus, a region with marked neuropathology in AD, was 15% of control values (10 AD patients and 4 control individuals). Western blot analysis indicated a large decrease in free PN-1 protein and an increase in PN-1-containing complexes that comigrated with PN-1 thrombin complexes. Northern blot analysis indicated that PN-1 mRNA levels were about equal in brains from AD patients and control individuals. Thus these results suggest that the decreases in PN-1 activity and free PN-1 protein are due to formation of PN-1-protease complexes.

Original languageEnglish
Pages (from-to)8284-8288
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - 1989

ASJC Scopus subject areas

  • General


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