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κ-卡拉胶寡糖通过调节阿尔茨海默病中的小胶质细胞自噬来保护神经。

κ-Carrageenan Oligosaccharides Protect Nerves by Regulating Microglial Autophagy in Alzheimer's Disease.

机构信息

College of Life health, Dalian University, No. 10 Xuefu Street, Dalian Economic and Technological Development Zone, Liaoning 116622, Dalian, China.

Department of Clinical Laboratory, Xinhua Hospital Affiliated to Dalian University, Liaoning 116021, Dalian, China.

出版信息

ACS Chem Neurosci. 2023 Sep 20;14(18):3540-3550. doi: 10.1021/acschemneuro.3c00460. Epub 2023 Aug 31.

Abstract

κ-Carrageenan is a linear sulfated polysaccharide extracted from the cell wall of marine red algae, and its enzymatically digested oligosaccharides (KOS) can inhibit microglial hyperactivation. Alzheimer's disease (AD) is a common chronic neurodegenerative disease, characterized by cognitive and memory impairment accompanied by nerve cell damage. Microglia activation causing enhancement of proinflammatory effects and neurotoxicity is one of the early events in AD disease. In this study, whether KOS have therapeutic or preventive effects in the AD model prepared from APP/PS1 transgenic mice was determined. Learning and memory of AD mice were detected by water maze experiments, and microglial activation-related protein expression and deposition of APP and Aβ in the brain were examined. The effects of KOS on expressed inflammatory factors and inflammation-related proteins by microglia were tested by cell experiments. Transwell coculture was used to investigate the effect of microglia on neural cell activity after KOS treatment. The results showed that KOS could relieve the clinical symptoms in AD mice, and a decrease in the expression of inflammatory factors and inflammation-related proteins in brain tissue was detected. KOS alleviated nerve cell apoptosis by inhibiting the overactivation of microglia, thus exhibiting neuroprotective effects. Exploring the protective effect of KOS inhibition of microglia inflammation is expected to provide a theoretical basis for KOS as a therapeutic drug for neurodegenerative diseases.

摘要

κ-卡拉胶是一种从海洋红藻细胞壁中提取的线性硫酸化多糖,其酶解寡糖(KOS)可以抑制小胶质细胞的过度激活。阿尔茨海默病(AD)是一种常见的慢性神经退行性疾病,其特征是认知和记忆障碍,伴有神经细胞损伤。小胶质细胞的激活导致促炎作用和神经毒性增强是 AD 疾病的早期事件之一。在这项研究中,确定了 KOS 对 APP/PS1 转基因小鼠制备的 AD 模型是否具有治疗或预防作用。通过水迷宫实验检测 AD 小鼠的学习和记忆,检查大脑中与小胶质细胞激活相关的蛋白表达和 APP 和 Aβ的沉积。通过细胞实验测试 KOS 对小胶质细胞表达的炎症因子和炎症相关蛋白的影响。使用 Transwell 共培养来研究 KOS 处理后小胶质细胞对神经细胞活性的影响。结果表明,KOS 可以缓解 AD 小鼠的临床症状,并检测到脑组织中炎症因子和炎症相关蛋白的表达减少。KOS 通过抑制小胶质细胞的过度激活来减轻神经细胞凋亡,从而表现出神经保护作用。探索 KOS 抑制小胶质细胞炎症的保护作用有望为 KOS 作为神经退行性疾病治疗药物提供理论依据。

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