Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity

International Journal of Molecular Sciences

Xueling Dai²  Wanqi Hou¹  Yaxuan Sun²  Zhaolan Gao²  Shigong Zhu³  Zhaofeng Jiang² 

[1] College of Life Sciences, Capital Normal University, Beijing 100048, China; E-Mail:;Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China; E-Mails:;Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China; E-Mail:

关键词: Alzheimer’s disease;    amyloid-β peptide;    chitosan oligosaccharides;    aggregation;    neurotoxicity;   

DOI  :  10.3390/ijms160510526

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.