Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity.
Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity.
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DOI：
10.3390/ijms160510526
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发表时间：
2015-05-08
影响因子：
5.6
通讯作者：
Jiang Z
中科院分区：
文献类型：
--
作者：
Dai X;Hou W;Sun Y;Gao Z;Zhu S;Jiang Z
阿尔茨海默氏病 (AD) 的特点是大脑中存在大量β淀粉样蛋白 (Aβ) 沉积。因此，抑制 Aβ 聚集或破坏预先形成的聚集体的稳定性可能是阻止/减缓 AD 进展的一个有前景的治疗靶点。此前已有报道称壳寡糖（COS）具有抗氧化和神经保护作用。最近的研究表明，COS 可以显着降低寡聚 Aβ 诱导的大鼠海马神经元的神经毒性和氧化应激。然而，COS 降低 Aβ 介导的神经毒性的潜在机制仍不清楚。在本研究中，我们从圆二色光谱、透射电子显微镜和硫代黄素 T 荧光测定中得到的结果表明，COS 可以作为 Aβ 聚集的抑制剂，并且这种作用表现出剂量依赖性。此外，硫黄素 T 测定的数据表明，COS 可以显着抑制原纤维形成并以剂量依赖性方式破坏已形成的原纤维。此外，添加 COS 可以减轻 Aβ1-42 诱导的大鼠皮质神经元的神经毒性。综上所述，我们的结果首次证明 COS 可以抑制 Aβ1-42 原纤维形成并分解预先形成的原纤维，这表明 COS 可能具有抗 Aβ 原纤维形成和原纤维不稳定的特性。这些发现强调了 COS 作为预防和治疗 AD 的新型治疗剂的潜在作用。
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.
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影响因子：
168.9
作者：
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通讯作者：
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