College of Ocean and Meteorology, Guangdong Ocean University, Zhanjiang 524088, China.
College of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, China.
Mar Drugs. 2017 Nov 7;15(11):322. doi: 10.3390/md15110322.
Classic hypotheses of Alzheimer's disease (AD) include cholinergic neuron death, acetylcholine (ACh) deficiency, metal ion dynamic equilibrium disorder, and deposition of amyloid and tau. Increased evidence suggests neuroinflammation and oxidative stress may cause AD. However, none of these factors induces AD independently, but they are all associated with the formation of Aβ and tau proteins. Current clinical treatments based on ACh deficiency can only temporarily relieve symptoms, accompanied with many side-effects. Hence, searching for natural neuroprotective agents, which can significantly improve the major symptoms and reverse disease progress, have received great attention. Currently, several bioactive marine products have shown neuroprotective activities, immunomodulatory and anti-inflammatory effects with low toxicity and mild side effects in laboratory studies. Recently, chitosan (CTS), chitooligosaccharide (COS) and their derivatives from exoskeletons of crustaceans and cell walls of fungi have shown neuroprotective and antioxidative effects, matrix metalloproteinase inhibition, anti-HIV and anti-inflammatory properties. With regards to the hypotheses of AD, the neuroprotective effect of CTS, COS, and their derivatives on AD-like changes in several models have been reported. CTS and COS exert beneficial effects on cognitive impairments via inhibiting oxidative stress and neuroinflammation. They are also a new type of non-toxic β-secretase and AChE inhibitor. As neuroprotective agents, they could reduce the cell membrane damage caused by copper ions and decrease the content of reactive oxygen species. This review will focus on their anti-neuroinflammation, antioxidants and their inhibition of β-amyloid, acetylcholinesterase and copper ions adsorption. Finally, the limitations and future work will be discussed.
经典的阿尔茨海默病（AD）假说包括胆碱能神经元死亡、乙酰胆碱（ACh）缺乏、金属离子动态平衡紊乱和淀粉样蛋白和 tau 沉积。越来越多的证据表明神经炎症和氧化应激可能导致 AD。然而，这些因素都不能独立引起 AD，而是都与 Aβ和 tau 蛋白的形成有关。目前基于 ACh 缺乏的临床治疗方法只能暂时缓解症状，同时伴有许多副作用。因此，寻找能够显著改善主要症状和逆转疾病进程的天然神经保护剂已受到广泛关注。目前，一些具有生物活性的海洋产物在实验室研究中显示出神经保护、免疫调节和抗炎作用，且具有低毒性和轻微的副作用。最近，甲壳素（CTS）、壳寡糖（COS）及其衍生物，来自甲壳动物的外骨骼和真菌细胞壁，表现出神经保护和抗氧化作用、基质金属蛋白酶抑制、抗 HIV 和抗炎特性。就 AD 的假说而言，已有报道称 CTS、COS 及其衍生物对几种模型中的 AD 样变化具有神经保护作用。CTS 和 COS 通过抑制氧化应激和神经炎症对认知障碍产生有益影响。它们也是一种新型的无毒β-分泌酶和乙酰胆碱酯酶抑制剂。作为神经保护剂，它们可以减少铜离子引起的细胞膜损伤并降低活性氧的含量。本综述将重点介绍它们的抗神经炎症、抗氧化作用以及对β-淀粉样蛋白、乙酰胆碱酯酶和铜离子吸附的抑制作用。最后，将讨论其局限性和未来的工作方向。
