Quercetin attenuates tau hyperphosphorylation and improves cognitive disorder via suppression of ER stress in a manner dependent on AMPK pathway
Quercetin attenuates tau hyperphosphorylation and improves cognitive disorder via suppression of ER stress in a manner dependent on AMPK pathway
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DOI：
10.1016/j.jff.2016.01.036
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发表时间：
2016-04-01
影响因子：
5.6
通讯作者：
Ma, Shiping
中科院分区：
文献类型：
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作者：
Chen, Junjun;Deng, Xueyang;Ma, Shiping
槲皮素是一种富含洋葱、苹果、茶、浆果、花椰菜和红酒的天然类黄酮，已被证明对阿尔茨海默病有有益作用。我们的目的是研究其AMPK对tau过度磷酸化的活性，并探索与内质网（ER）应激相关的潜在机制。槲皮素和槲皮素-3- o -葡糖苷通过降低IRE1 α和PERK的磷酸化来抑制内质网应激，从而抑制TXNIP和NLRP3炎症小体的激活，最终减弱冈酸（OA）诱导的SH-SY5Y细胞的tau磷酸化。然而，转染SiRNA下调AMPK α 1/2可阻断对tau磷酸化的影响。此外，槲皮素可增强高脂饮食小鼠AMPK活性，抑制IRE1 α和PERK磷酸化、NLRP3表达和tau磷酸化，改善认知障碍。AMPK可能是连接内质网应激和tau磷酸化的关键角色，并介导槲皮素对认知障碍的影响。因此，槲皮素及其AMPK活性可能为治疗AD患者提供一种潜在的治疗策略。(C) 2016年Elsevier Ltd.出版
Quercetin, a natural flavonoid abundantly found in onions, apples, tea, berries, cauliflower, and red wine, has been demonstrated to exert beneficial effect on Alzheimer's disease. We aimed to investigate its AMPK activity on hyperphosphorylation of tau and explore the underlying mechanism associated with Endoplasmic reticulum (ER) stress. Quercetin and quercetin-3-O-glucuronide suppressed ER stress with decreased phosphorylation of IRE1 alpha and PERK, thereby inhibited TXNIP and NLRP3 inflammasome activation, ultimately attenuated tau phosphorylation in okadaic acid (OA) induced SH-SY5Y cells. However, the effect on tau phosphorylation was blocked by downregulation of AMPK alpha 1/2 with SiRNA transfection. Moreover, administration of quercetin enhanced AMPK activity, inhibited IRE1 alpha and PERK phosphorylation, NLRP3 expression and tau phosphorylation and improved cognitive disorder in mice exposed to high fat diets. AMPK may be a key player that links ER stress and tau phosphorylation and mediates quercetin's effect on cognitive disorder. Thus, quercetin and its AMPK activity may provide a potential therapeutic strategy for treatment of AD patients. (C) 2016 Published by Elsevier Ltd.