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Regulation of proBACE1 by glycosaminoglycans

Citation

Small, DH and Klaver, DW and Beckman, M, Regulation of proBACE1 by glycosaminoglycans, Neurodegenerative Diseases, 5, (3-4) pp. 206-208. (2008) [Review Several Works]

DOI: doi:10.1159/000113703

Abstract

The β-secretase (BACE1) is initially synthesized as a partially active zymogen containing a prodomain which can be further activated through proteolytic cleavage of the prodomain by a furin-like protease. The active site of BACE1 is large and although a number of high-affinity active-site inhibitors of BACE1 have been described, most of these compounds are large, polar and do not cross the blood-brain barrier. However, it may be possible to target other regions of the protein which regulate BACE1 allosterically. We have found that proBACE1 can be stimulated by relatively low concentrations (e.g. 1 μg/ml) of heparin. Heparin initially increases proBACE1 activity, probably by binding to the prodomain, which decreases steric inhibition at the active site. However, the heparin-activated zymogen also undergoes autocatalysis, which ultimately leads to a loss of enzyme activity. We speculate that proBACE1 can be regulated by endogenous heparan sulfate proteoglycans and that drugs which target this interaction may have value in the treatment of Alzheimer's disease. Copyright © 2008 S. Karger AG.

Item Details

Item Type:Review Several Works
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Neurochemistry
Objective Division:Health
Objective Group:Specific Population Health (excl. Indigenous Health)
Objective Field:Health Related to Ageing
UTAS Author:Small, DH (Professor David Small)
ID Code:53137
Year Published:2008
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2008-11-03
Last Modified:2008-11-03
Downloads:0

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