Heparin promotes beta-secretase cleavage of the Alzheimer's amyloid precursor protein.
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.
Leveugle
B
B
Faculty of Pharmacy, University of Alberta, Edmonton, Canada. leveugle@gpu.srv.ualberta.ca
Ding
W
W
Durkin
J T
JT
Mistretta
S
S
Eisle
J
J
Matic
M
M
Siman
R
R
Greenberg
B D
BD
Fillit
H M
HM
D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D006493:Heparin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human