Effects of galantamine on β-amyloid release and beta-site cleaving enzyme 1 expression in differentiated human neuroblastoma SH-SY5Y cells

被引：30

作者：

Li, Qianqian ^{[1
]}

Wu, Donglai ^{[2
]}

Zhang, Liming ^{[1
]}

Zhang, Yan ^{[1
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 1, Dept Neurol, Harbin, Peoples R China

[2] Harbin Vet Res Inst, Harbin, Peoples R China

来源：

EXPERIMENTAL GERONTOLOGY | 2010年 / 45卷 / 11期

基金：

黑龙江省自然科学基金;

关键词：

Galantamine; Amyloid precursor protein; BACE1; beta amyloid; NICOTINIC ACETYLCHOLINE-RECEPTORS; ALPHA-SECRETASE CLEAVAGE; PRECURSOR-PROTEIN; ALZHEIMERS-DISEASE; METABOLISM; KINASE; INVOLVEMENT; PEPTIDE; BRAIN;

D O I：

10.1016/j.exger.2010.06.008

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Galantamine (Gal) is an acetylcholinesterase inhibitor and used to treat the symptoms of Alzheimer s disease (AD) Recent studies show that Gal may affect amyloid precursor protein (APP) metabolism and increase release of secretory APP alpha (sAPP alpha) However the effect of Gal on amyloid-beta peptide (A beta) release and beta-site cleaving enzyme 1 (BACE1) expression is still unknown. Consequently we investigated the effect of Gal on the level of A beta and BACE1 In a differentiated human neuroblastoma cell line (SH-SY5Y) Gal (0 3 mu M) was found to significantly decrease A beta release and BACE1 expression following treatment for 6 12 and 24 h Increasing Gal to 0 9 mu M or 10 pm had no further effect. The effect of Gal (0 3 mu M for 18 h) was maximal on BACE1 expression but not on A beta secretion At higher concentration (0 9 mu M and 10 mu M) Gal had no effect on the level of full-length APP but could still stimulate further decrease in A beta secretion and release of sAPP alpha These observations suggested that 0 3 mu M Gal exerts its effect on A beta production by inhibiting BACE1 expression while 0 9 mu M or 10 mu M Gal mainly reduces A beta production by stimulating the non-amyloidogenic pathway to decrease the amount of APP substrate available for beta-secretase cleavage In addition alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) and multiple second messengers (including PKC, MEK and p38MAPK) were found to be involved in the regulation of Gal inhibited A beta release and BACE1 expression (C) 2010 Elsevier Inc All rights reserved

引用

页码：842 / 847

页数：6

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