Chang Lan, Li Fushun, Chen Xiaowei, Xu Shujun, Wang Chuang, Chen Hongzhuan, Wang Qinwen
Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School, Ningbo University, Ningbo, 315211, China,
Metab Brain Dis. 2014 Sep;29(3):683-90. doi: 10.1007/s11011-014-9521-8. Epub 2014 Apr 11.
Soluble amyloid-β protein (Aβ) oligomers have been recognized to be early and key intermediates in Alzheimer's disease-related synaptic dysfunction. In this study, using in vitro electrophysiology, we investigated interactions of the acidic oligosaccharide sugar chain (AOSC), a marine-derived acidic oligosaccharide, with oligomeric Aβ. We found that the inhibition of long-term potentiation (LTP) induced by Aβ oligomers can be dose dependently reversed by the application of AOSC, whereas AOSC alone did not alter normal LTP induction. Interestingly, treatment with Aβ monomers with or without AOSC did not affect LTP induction. Additionally, when fresh-made Aβ was co-incubated with AOSC before in vitro testing, there was no impairment of LTP induction. The results from Western blots demonstrated that AOSC prevent the aggregation of Aβ oligomers. These findings indicate that AOSC may reverse Aβ oligomer-mediated cytotoxicity by directly disrupting the amyloid oligomer aggregation, and this action is concentration dependent. Thus, we propose that AOSC might be a potential therapeutic drug for Alzheimer's disease due to its protection against oligomeric Aβ-induced dysfunction of synaptic plasticity.
可溶性淀粉样β蛋白（Aβ）寡聚体已被公认为是阿尔茨海默病相关突触功能障碍的早期关键中间体。在本研究中，我们利用体外电生理学方法，研究了一种海洋来源的酸性寡糖——酸性寡糖糖链（AOSC）与寡聚体Aβ的相互作用。我们发现，应用AOSC可剂量依赖性地逆转Aβ寡聚体诱导的长时程增强（LTP）抑制，而单独使用AOSC不会改变正常的LTP诱导。有趣的是，用Aβ单体处理，无论有无AOSC，均不影响LTP诱导。此外，在体外测试前将新制备的Aβ与AOSC共同孵育，LTP诱导未受损害。蛋白质免疫印迹结果表明，AOSC可防止Aβ寡聚体的聚集。这些发现表明，AOSC可能通过直接破坏淀粉样寡聚体聚集来逆转Aβ寡聚体介导的细胞毒性，且这种作用具有浓度依赖性。因此，我们认为AOSC可能是一种潜在的治疗阿尔茨海默病的药物，因为它能保护突触可塑性免受寡聚体Aβ诱导的功能障碍。
