Leptin signaling plays a critical role in the geniposide-induced decrease of tau phosphorylation.
We have previously demonstrated that geniposide attenuates the production of Aβ1-42 both in vitro and in vivo via enhancing leptin receptor signaling. But the role played by geniposide in the phosphorylation of tau and its underlying molecular mechanisms remain unclear. In this study, we investigated the effect of geniposide on the phosphorylation of tau and the role of leptin signaling in this process. Our data suggested that, accompanied by the up-regulation of leptin receptor expression, geniposide significantly decreased the phosphorylation of tau in rat primary cultured cortical neurons and in APP/PS1 transgenic mice, and this geniposide-induced decrease of tau phosphorylation could be prevented by leptin antagonist (LA). Furthermore, LA also prevented the phosphorylation of Akt at Ser-473 site and GSK-3β at Ser-9 site induced by geniposide. All these results indicate that geniposide may regulate tau phosphorylation through leptin signaling, and geniposide may be a promising therapeutic compound for the treatment of Alzheimer's disease in the future.
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China Chongqing Key Lab of Catalysis & Functional Organic Molecules, Chongqing Technology and Business University, Chongqing 400067, China.
Jianhui
J
Liu
Chongqing Key Lab of Catalysis & Functional Organic Molecules, Chongqing Technology and Business University, Chongqing 400067, China.
Zixuan
Z
Liu
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.
Yonglan
Y
Zhang
College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China Chongqing Key Lab of Catalysis & Functional Organic Molecules, Chongqing Technology and Business University, Chongqing 400067, China fyin@cqut.edu.cn.
Fei
F
Yin
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D039823:Iridoids / Q000737:chemistry*; D020738:Leptin / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction; D016875:tau Proteins / Q000737:chemistry*
D039823:Iridoids; D020738:Leptin; C558298:Mapt protein, mouse; C489131:Mapt protein, rat; D054411:Receptors, Leptin; D016875:tau Proteins; C007835:geniposide; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat
Alzheimer's disease; GSK-3β; geniposide; leptin; tau