title: Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity.
abstract: Alzheimer's disease (AD) is characterized by a large number of amyloid-β (Aβ) deposits in the brain. Therefore, inhibiting Aβ 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 Aβ-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce Aβ-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 Aβ 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 Aβ1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit Aβ1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-Aβ fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD.
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China. xueling@buu.edu.cn.
authors.forename: Xueling
authors.initials: X
authors.lastname: Dai
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing 100048, China. bluefire828@126.com.
authors.forename: Wanqi
authors.initials: W
authors.lastname: Hou
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China. sunxx@buu.edu.cn.
authors.forename: Yaxuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China. zhaolan@buu.edu.cn.
authors.forename: Zhaolan
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China. sgzhu@bjmu.edu.cn.
authors.forename: Shigong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China. zfjiang6@gmail.com.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000031:analogs & derivatives / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000648:ultrastructure; D066329:Protein Aggregates / Q000187:drug effects; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D009844:Oligosaccharides; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); D048271:Chitosan
keywords: Alzheimer’s disease; aggregation; amyloid-β peptide; chitosan oligosaccharides; neurotoxicity