RGD Reference Report - Protease nexin-1, an antithrombin with neurite outgrowth activity, is reduced in Alzheimer disease. - Rat Genome Database

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

Authors: Wagner, SL  Geddes, JW  Cotman, CW  Lau, AL  Gurwitz, D  Isackson, PJ  Cunningham, DD 
Citation: Wagner SL, etal., Proc Natl Acad Sci U S A. 1989 Nov;86(21):8284-8.
RGD ID: 2317937
Pubmed: PMID:2813392   (View Abstract at PubMed)
PMCID: PMC298265   (View Article at PubMed Central)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  IDA 2317937 RGD 
Alzheimer's disease  ISOSERPINE2 (Homo sapiens)2317937; 2317937 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine2  (serpin family E member 2)

Genes (Mus musculus)
Serpine2  (serine (or cysteine) peptidase inhibitor, clade E, member 2)

Genes (Homo sapiens)
SERPINE2  (serpin family E member 2)


Additional Information