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Heparin promotes beta-secretase cleavage of the Alzheimer's amyloid precursor protein. 1997
B Leveugle, and
W Ding, and
J T Durkin, and
S Mistretta, and
J Eisle, and
M Matic, and
R Siman, and
B D Greenberg, and
H M Fillit
Faculty of Pharmacy, University of Alberta, Edmonton, Canada. leveugle@gpu.srv.ualberta.ca
In Alzheimer's disease, abnormal processing of the amyloid precursor protein (APP) is thought to play an important role in amyloid deposition. We investigated the effect of heparin, a highly sulfated glycosaminoglycan related to heparan sulfate, on the secretion of the beta-secretase cleavage product of APP (sAPP beta) in a human neuroblastoma cell line. Heparin induced an increase in the secretion of total APP, and an even greater relative increase in the secretion of sAPP beta. The effect on sAPP beta was specific to heparin. These data support the hypothesis that highly sulfated heparan sulfate proteoglycans may promote amyloidogenic pathways of APP metabolism.
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