Leveugle B, Ding W, Durkin J T, Mistretta S, Eisle J, Matic M, Siman R, Greenberg B D, Fillit H M
Faculty of Pharmacy, University of Alberta, Edmonton, Canada.
Neurochem Int. 1997 Jun;30(6):543-8. doi: 10.1016/s0197-0186(96)00103-9.
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.
在阿尔茨海默病中，淀粉样前体蛋白（APP）的异常加工被认为在淀粉样沉积中起重要作用。我们研究了肝素（一种与硫酸乙酰肝素相关的高度硫酸化糖胺聚糖）对人神经母细胞瘤细胞系中APP的β-分泌酶裂解产物（sAPPβ）分泌的影响。肝素诱导总APP分泌增加，且sAPPβ分泌的相对增加更大。对sAPPβ的影响是肝素特有的。这些数据支持了高度硫酸化的硫酸乙酰肝素蛋白聚糖可能促进APP代谢的淀粉样生成途径这一假说。
