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

International Journal of Molecular Sciences

Xueling Dai¹  Zhaolan Gao¹  Yaxuan Sun¹  Zhaofeng Jiang¹  Wanqi Hou²  Shigong Zhu³ 

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

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

DOI  :  10.3390/ijms160510526

来源: DOAJ

【 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 thatCOS act as an inhibitor of Aβ aggregation and this effect shows dose-dependency.Moreover, data from thioflavin T assay indicated that COS could significantlyinhibit 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 COSmay 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】

Unknown