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Association and Release of the Amyloid Protein Precursor of Alzheimer's Disease from Chick Brain Extracellular Matrix
Citation
Small, DH and Nurcombe, V and Moir, R and Michaelson, S and Monard, D and Beyreuther, K and Masters, CL, Association and Release of the Amyloid Protein Precursor of Alzheimer's Disease from Chick Brain Extracellular Matrix, Journal of Neuroscience, 12, (11) pp. 4143-4150. ISSN 0270-6474 (1992) [Refereed Article]
Abstract
The amyloid protein precursor (APP) of Alrheimer’s disease
was found to bind saturably (K, = 60 nM) to embryonic chick
brain extracellular matrix (ECM). The binding of APP to ECM
was not inhibited by 10 pglml heparin or heparan sulfate.
However, pretreatment of cells with 1 mr.! 4-methylumbelliferyl-@-
D-XylOSide, an inhibitor of proteoglycan biosynthesis,
reduced the number of APP binding sites on the ECM by
60%. The binding of APP to ECM was also inhibited by pretreatment
with chlorate, an inhibitor of glycan sulfation, and
heparitinase, which digests the carbohydrate component of
heparan sulfate proteoglycans. These results suggest that
APP binds with high affinity to one or more heparan sulfate
proteoglycans. Acidic and basic fibroblast growth factor
(FGF) also bound to chick ECM. When ECM was incubated
with a protease associated with the enzyme AChE (AChEAP),
APP and acidic FGF were released intact from the matrix.
The AChE-AP was at least IOO-fold more potent in releasing
APP from ECM than other trypsin-like proteases
(trypsin, plasmin, thrombin). The action of the AChE-AP was
inhibited by glia-derived nexin (protease nexin I) and by human
brain APP at low nanomolar concentrations. These results
suggest that in viwo an AChE-AP may cleave ECM proteins
to regulate the availability of soluble APP or other factors
bound to the ECM.
Item Details
Item Type: | Refereed Article |
---|---|
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Neurosciences |
Research Field: | Neurosciences not elsewhere classified |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Small, DH (Professor David Small) |
ID Code: | 71704 |
Year Published: | 1992 |
Web of Science® Times Cited: | 84 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2011-08-02 |
Last Modified: | 2011-08-02 |
Downloads: | 0 |
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