摘要
阿尔茨海默病(阿尔茨海默病)是一种最常见的神经退行性疾病,其特征是海马和大脑皮质中淀粉样-β(Aβ)肽的聚集。炎症被认为是AD的认知功能下降的发展驱动力的炎症反应过程中,激活的星形胶质细胞和小胶质细胞诱导的Aβ肽产生促炎因子和毒素,促进AD脑部神经退行性疾病、老年痴呆症。因此,抑制胶质细胞过度激活在广告大脑可能会导致治疗效果。雷公藤甲素,从中药雷公藤中提取的一种天然化合物,具有抗炎作用。雷公藤内酯醇对AD样是否具有通过抗炎作用病理的预防作用尚不清楚。目前的研究表明,腹腔注射雷公藤甲素(20μg/kg)15周显著减轻学习和记忆缺陷问题,并在AD转基因小鼠脑阻止Aβ积累(APP/PS1小鼠)。这些结果都伴随着对APP/PS1小鼠雷公藤内酯醇相比APP/PS1小鼠生理盐水治疗脑胶质细胞的激活和炎症因子含量减少。此外,我们观察到有丝分裂原活化蛋白激酶(MAPK p38、ERK和JNK)磷酸化也在APP/PS1小鼠大脑中的雷公藤甲素治疗抑制。总之,我们的研究表明,分子机制研究雷公藤甲素对AD模型的治疗作用可能是通过抑制蛋白激酶活性的抑制炎症反应。
关键词: 阿尔茨海默病、ERK、JNK、p38、炎症、雷公藤内酯醇。
Current Alzheimer Research
Title:Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice
Volume: 13 Issue: 3
Author(s): Yan-Qiu Cui, Qi Wang, Dong-Mei Zhang, Jun-Ya Wang, Bing Xiao, Yan Zheng, Xiao-Min Wang
Affiliation:
关键词: 阿尔茨海默病、ERK、JNK、p38、炎症、雷公藤内酯醇。
摘要: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by aggregation of amyloid-β (Aβ) peptide in the hippocampus and cortex of brain. Neuroinflammation is considered a driving force of the progression of cognitive decline in AD. During the neuroinflammatory process, activated astrocytes and microglia induced by Aβ peptide produce pro-inflammatory factors and neurotoxins, which promote neurodegeneration in AD brain, eventually dementia. Thus, the suppression of glial over-activation in AD brain might result in therapeutic effect. Triptolide, a natural compound extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F., has shown anti-inflammatory effects. Whether triptolide exhibits preventive effects on AD-like pathology via anti-inflammatory action is unclear. The present study showed that intraperitoneal injection of triptolide (20 μg/kg) for 15 weeks markedly alleviated deficits in learning and memory, and prevented Aβ accumulation in the brain of AD transgenic mice (APP/PS1 mice). These results were accompanied by reduction in glial activation and contents of pro-inflammatory factors in the brain of APP/PS1 mice treated by triptolide compared to saline-treated APP/PS1 mice. In addition, we observed that the Mitogen-activated protein kinases (MAPKs, including p38, ERK and JNK) phosphorylation was also suppressed by treatment of triptolide in the brain of APP/PS1 mice. Taken together, our study suggests that molecular mechanisms underlying the therapeutic effects of triptolide on the AD model might involve inhibition of the neuroinflammation by suppressing MAPKs activity.
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Yan-Qiu Cui, Qi Wang, Dong-Mei Zhang, Jun-Ya Wang, Bing Xiao, Yan Zheng, Xiao-Min Wang , Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice, Current Alzheimer Research 2016; 13 (3) . https://dx.doi.org/10.2174/156720501303160217122803
DOI https://dx.doi.org/10.2174/156720501303160217122803 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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