Upregulation of AMPK Ameliorates Alzheimer's Disease-Like Tau Pathology and Memory Impairment.
The studies have shown that 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is involved in Alzheimer's disease (AD) pathology, but the effects of AMPK on AD-like Tau abnormal phosphorylation and its underlying mechanism remains unclear. Herein, we found that the mRNA expression and activity of AMPK are significantly decreased in the brains of the aging C57 mice and 3 × Tg AD mice when compared with their respective control. Moreover, when downregulation of AMPK with AAV-siAMPK-eGFP in the hippocampus CA3 of 3-month-old C57 mice, the mice display AD-like Tau hyperphosphorylation, fear memory impairment, and glycogen synthase kinase-3β (GSK3β) activity increased. On the other hand, there are also AD-like Tau hyperphosphorylation, impairment of fear memory, and AMPK activity decreased in streptozotocin (STZ) mice. Interestingly, AMPK overexpression could efficiently rescue AD-like Tau phosphorylation and brain impairment in STZ mice. Moreover, the activity of GSK3β and the level of Tau phosphorylation (Ser396 and Thr231 sites) were significantly decreased in HEK293 Tau cells transfected by AMPK plasmid or treated with agonists salicylate (SS), but GSK3β agonists Wortmannin (Wort) could ablate AMPK-mediated Tau dephosphorylation. Taken together, the study indicated that AMPK reduces Tau phosphorylation and improves brain function and inhibits GSK3β in AD-like model. These findings proved that AMPK might be a new target for AD in the future.
['Wang|Lin|L|', 'Li|Na|N|', 'Shi|Fang-Xiao|FX|', 'Xu|Wei-Qi|WQ|', 'Cao|Yun|Y|', 'Lei|Ying|Y|', 'Wang|Jian-Zhi|JZ|', 'Tian|Qing|Q|', 'Zhou|Xin-Wen|XW|http://orcid.org/0000-0003-1357-7039']
D055372:AMP-Activated Protein Kinases D000375:Aging D000544:Alzheimer Disease D000818:Animals D006624:Hippocampus D008568:Memory D008569:Memory Disorders D008810:Mice, Inbred C57BL D010766:Phosphorylation D016875:tau Proteins
AMPK Tau GSK3β Alzheimer’s disease