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Association and Release of the Amyloid Protein Precursor of Alzheimer's Disease from Chick Brain Extracellular Matrix


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]


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

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