文献类型：期刊文献

英文题名：Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid beta-Mediated Neurotoxicity

作者：Dai, Xueling[1];Hou, Wanqi[2];Sun, Yaxuan[1];Gao, Zhaolan[1];Zhu, Shigong[3];Jiang, Zhaofeng[1]

第一作者：戴雪伶

通讯作者：Jiang, ZF[1]

机构：[1]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China;[2]Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China;[3]Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China

第一机构：北京联合大学应用文理学院|北京联合大学生物化学工程学院

通讯机构：[1]corresponding author), Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;[114172]北京联合大学应用文理学院;

年份：2015

卷号：16

期号：5

起止页码：10526-10536

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-84929353020);WOS:【SCI-EXPANDED(收录号:WOS:000356241400084)】；

基金：This work was supported by grants from NSFC Project 31071512, and grants from Scientific Research Common Program of Beijing Municipal Commission of Education (SQKM201511417013). We gratefully thank Lin Yang (Institute of Genetics and Developmental Biology, Chinese Academy of Sciences) for her technical help with the use of TEM.

语种：英文

外文关键词：Alzheimer's disease; amyloid- peptide; chitosan oligosaccharides; aggregation; neurotoxicity

摘要：Alzheimer's disease (AD) is characterized by a large number of amyloid- (A) deposits in the brain. Therefore, inhibiting A aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects. Recent study shows that COS could markedly decrease oligomeric A-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce A-mediated neurotoxicity remains unclear. In the present study, our findings from circular dichroism spectroscopy, transmission electron microscope and thioflavin T fluorescence assay suggested that COS act as an inhibitor of A aggregation and this effect shows dose-dependency. Moreover, data from thioflavin T assay indicated that COS could significantly inhibit fibrils formation and disrupt preformed fibrils in a dose-dependent manner. Furthermore, the addition of COS attenuated A1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit A1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-A fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD.