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

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

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
Volume86
Issue number21
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General

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