文献类型：期刊文献

英文题名：The inhibitory effect of chitosan oligosaccharides on beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in HEK293 APPswe cells

作者：Dai, Xueling[1];Chang, Ping[1];Li, Xiaoxiao[1];Gao, Zhaolan[2];Sun, Yaxuan[2]

第一作者：戴雪伶

通讯作者：Dai, XL[1];Sun, YX[2]

机构：[1]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China;[2]Beijing Union Univ, Coll Biochem Engn, Dept Food Sci, Beijing 100023, Peoples R China

第一机构：北京联合大学生物化学工程学院|北京联合大学应用文理学院

通讯机构：[1]corresponding author), Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China;[2]corresponding author), Beijing Union Univ, Coll Biochem Engn, Dept Food Sci, Beijing 100023, Peoples R China.|[11417146]北京联合大学生物化学工程学院食品科学系;[11417]北京联合大学;[1141726]生物化学工程学院;[114172]北京联合大学应用文理学院;

年份：2018

卷号：665

起止页码：80-85

外文期刊名：NEUROSCIENCE LETTERS

收录：;Scopus(收录号：2-s2.0-85034976085);WOS:【SCI-EXPANDED(收录号:WOS:000426235500015)】；

基金：This work was supported by grants from Beijing Natural Science Foundation (6164030), Scientific Research Common Program of Beijing Municipal Commission of Education (SQKM201511417013), Beijing Municipal Outstanding Talent Training Funding (2015000020124G049), and Scientific Research Project from Facing Characteristic Discipline of BUU (KYDE40201703).

语种：英文

外文关键词：Alzheimer's disease; beta-Amyloid peptide; Chitosan oligosaccharides; beta-Site amyloid precursor protein cleaving; enzyme 1 (BACE1)

摘要：Amyloid precursor protein (APP) proteolysis is essential for the production of beta-amyloid peptides (A beta) that form senile plaques in Alzheimer's disease (AD) brains. The beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) is the rate limiting enzyme in the generation of A beta from APP, inhibition of BACE1 is thereby considered as an attractive strategy for anti-AD drug discovery. Chitosan oligosaccharides (COS) has been shown to possess various biological activities. Here we investigated the potential inhibitory effect of COS on both BACE1 expression in HEK293 APPswe cells and BACE1 enzymatic activity in vitro. The results showed that COS (100-500 mu g/ml) dose-dependently decreased the cell apoptosis, and potently repressed the secretion of both A beta 40 and A beta 42 as determined by ELISA. Moreover, treatment with COS resulted in a dramatic reduction in BACE1 mRNA and protein expression level, eIF2 alpha phosphorylation as well as BACE1 enzymatic activity. Taken together, our findings indicate that COS can ameliorate A beta-associated neurotoxicity, which may be, at least in part, attributable to reductions in BACE1 enzymatic activity and expression.