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Decreases in protease nexins in Alzheimer's disease brain.

Abstract
A marked and significant reduction of protease nexin-1 (PN-1) and PN-2/amyloid beta protein precursor (A beta PP) was observed in selected regions of Alzheimer's disease (AD) brains as compared to those of aged-matched controls. Correlative analysis indicated a relationship between PN-1 reduction and the severity of pathologic alterations. A statistically significant inverse correlation was noted between the level of PN-1 activity and the density of tau-positive dystrophic neurites in the hippocampus. In view of the ability of thrombin and PN-1 activity to regulate neurite outgrowth, it is possible that abnormal thrombin and PN-1 interactions may play a role in dystrophic neurite formation. The presence of clusters of dystrophic neurites around the capillaries suggests that blood-brain barrier (BBB) dysfunction may enhance such abnormal interactions. The decrease in PN-2/A beta PP levels in AD brains could possibly contribute to neuronal degeneration in AD in view of the ability of PN-2/A beta PP to protect neurons against the toxic effects of the A beta.
AuthorsB H Choi, R C Kim, P J Vaughan, A Lau, W E Van Nostrand, C W Cotman, D D Cunningham
JournalNeurobiology of aging (Neurobiol Aging) 1995 Jul-Aug Vol. 16 Issue 4 Pg. 557-62 ISSN: 0197-4580 [Print] United States
PMID8544905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amyloid beta-Protein Precursor
  • Carrier Proteins
  • Protease Nexins
  • Receptors, Cell Surface
  • SERPINE2 protein, human
  • Serpin E2
  • tau Proteins
  • Thrombin
Topics
  • Aged
  • Alzheimer Disease (enzymology, pathology)
  • Amyloid beta-Protein Precursor (metabolism)
  • Blotting, Western
  • Brain (enzymology, pathology)
  • Carrier Proteins (metabolism)
  • Hippocampus (enzymology, pathology)
  • Humans
  • Neurites (enzymology, pathology)
  • Protease Nexins
  • Receptors, Cell Surface
  • Regression Analysis
  • Serpin E2
  • Thrombin (metabolism)
  • tau Proteins (metabolism)

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