Mazzucchelli M, Porrello E, Villetti G, Pietra C, Govoni S, Racchi M
Department of Experimental and Applied Pharmacology, University of Pavia, Pavia, Italy.
J Neural Transm (Vienna). 2003 Aug;110(8):935-47. doi: 10.1007/s00702-003-0006-x.
We have investigated the effect of ganstigmine (CHF2819), a novel geneserine derived acetylcholinesterase (AChE) inhibitor, on the expression and metabolism of the amyloid precursor protein (APP) in neuroblastoma cell line SH-SY5Y. The rationale was based on the suggestion that cholinergic activity may also be involved in the regulation of APP metabolism. We studied the acute effect on APP metabolism following the secretion of sAPPalpha in the conditioned medium of cells. Following short term treatment (2h), ganstigmine promoted a slight increase in the release of sAPPalpha, the maximal effect approaching on average 1.5 fold baseline value. The data obtained in the long term experiments demonstrate that continuous inhibition of AchE obtained with 100 nM ganstigmine following an exposure of 24 hours did not influence APP isoforms expression. However, the compound appeared to increase the constitutive release of sAPPalpha, with a mechanism that is derived from an indirect cholinergic stimulation.
我们研究了新型基因丝氨酸衍生的乙酰胆碱酯酶（AChE）抑制剂加奈斯的明（CHF2819）对神经母细胞瘤细胞系SH-SY5Y中淀粉样前体蛋白（APP）表达和代谢的影响。其理论依据是胆碱能活性可能也参与APP代谢的调节这一观点。我们研究了细胞条件培养基中分泌sAPPα后对APP代谢的急性影响。短期处理（2小时）后，加奈斯的明促使sAPPα释放略有增加，最大效应平均接近基线值的1.5倍。长期实验获得的数据表明，在暴露24小时后用100 nM加奈斯的明持续抑制乙酰胆碱酯酶并不影响APP亚型的表达。然而，该化合物似乎增加了sAPPα的组成性释放，其机制源于间接胆碱能刺激。
