期刊
JOURNAL OF FUNCTIONAL FOODS
卷 22, 期 -, 页码 463-476出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jff.2016.01.036
关键词
AMPK; ER stress; NLRP3 inflammasome; Quercetin; Quercetin-3-O-glucuronide; Tau phosphorylation
资金
- National Natural Science Foundation of China [81573701]
- College Students Innovation Project for the RAMP
- D of Novel Drugs [J1030830]
- National Undergraduate Innovative Entrepreneurship Training Programs
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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.
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